Defending US Open champion Dominic Thiem will miss this year's tournament with a wrist injury that will rule him out until 2022.

The 27-year-old suffered the setback at the Mallorca Open in June and also withdrew from Wimbledon and the Tokyo Olympics.

World number six Thiem won his maiden grand slam at Flushing Meadows last year with victory over Alexander Zverev in a five-set thriller, but he will not get the chance to defend his title in New York.

"Having spent a week training on court, I still felt pain in my wrist and I knew that it was not 100 per cent," Thiem posted in a statement on his Twitter page on Wednesday.

"I went to see my doctors again and we have decided to follow a conservative treatment, giving the injury more time to recover.

"I'm very disappointed not to be able to defend my US Open title and to miss the rest of the season.

"But I know this is what I have to do. I have a long career ahead of me, so I will only come back once I'm fully recovered and in good shape to compete."

Thiem has a record of nine wins and nine losses this season, with his best result coming at the Madrid Open in May when reaching the semi-finals.

Twenty-time grand slam winner Roger Federer last week pulled out of the US Open, which runs from August 30 until September 12, after undergoing knee surgery.

Fifth seed Matteo Berrettini survived an early scare on his return from a thigh injury to progress in the second round of the Western and Southern Open in Cincinnati over Albert Ramos-Vinolas on Tuesday.

The Italian world number eight, making his ATP Tour return since losing the Wimbledon final to Novak Djokovic in July, won 6-7 (5-7) 6-3 7-5.

The Spaniard claimed the first set in a tie-break but Berrettini hit back, sending down 25 aces for the match, winning 84 per cent on his first serve.

"I'm happy for the win. I think I served really well," Berrettini said. "My strokes from the baseline weren't working the way I wanted them to, but I knew from the beginning it's been a long time since I played a match, especially on hard, so I expected to feel a little bit weird."

The match extended to two hours and 20 minutes, with the Italian utilizing his backhand slice in the final set to get the edge.

Berrettini, who has a 33-7 record for the season, will face 12th seed Felix Auger-Aliassime or Karen Khachanov in the third round.

"I'm really happy that I'm going to have the chance to play another match because that's what I need," Berrettini said. "I need to play matches. I need to get in the best shape possible."

Canadian sixth seed Denis Shapovalov suffered a shock early upset, going down to France's Benoit Paire 6-3 4-6 7-5 in the Round of 64.

Former US Open, Wimbledon and Australian Open semi-finalist Grigor Dimitrov toppled 13th seed Roberto Bautista Agut 6-3 6-4 in one hour and 21 minutes.

Fellow seed Cristian Garin also bowed out, losing 4-6 6-3 6-4 to qualifier Tommy Paul, while ninth seed Hubert Hurkacz defeated Alejandro Davidovich Fokina 6-1 6-7 (3-7) 6-1.

Marin Cilic, John Isner, Sebastian Korda, Gael Monfils, Reilly Opelka, Lorenzo Sonego and Frances Tiafoe were the other Tuesday winners.

Isner sent down his 13,000th career ace in his three-set win over Briton Cam Norrie.

Stefanos Tsitsipas has indicated he will only get the COVID-19 vaccine if it becomes mandatory to participate on the ATP Tour.

World number three Tsitsipas revealed he has not yet been jabbed against coronavirus with the tennis world divided on the issue. 

The ATP Tour have publicly encouraged players to get vaccinated, but Novak Djokovic is among the high-profile players to have stated it should not be compulsory to compete.

When asked ahead of the Western and Southern Open if he would get the vaccine, Tsitsipas told a media conference he still had reservations.

"No one has told me anything. No one has made it a mandatory thing to be vaccinated," the Greek said.

"At some point I may have to, I'm pretty sure about it, but so far it hasn't been mandatory to compete, so I haven't done it, no."

Tsitsipas received a bye through to the second round in Cincinnati, where he will play either Sebastian Korda or Laslo Dere.

The 23-year-old, who has a tour-high 45 wins this season, climbed up to third in the world rankings last week and boldly targeted overhauling Djokovic in top spot.

"The rankings are there for a reason. They signify something important," he added.

"I think that the very next step would be the number one spot, which I hope I can get to one day.”

Andy Murray looked sharp in his first singles match since Wimbledon, rolling to a straight-sets win over Richard Gasquet at the Western and Southern Open. 

Murray defeated the veteran Frenchman 6-4 6-4 on a rainy opening day in Cincinnati, capitalising on a strong service game to advance. 

Murray had 14 aces to just two double faults and won 81 per cent of points on his first serve while saving four of the five break points he faced. 

A two-time champion at the ATP 1000 event, he will face the winner of Tuesday's match between Alejandro Davidovich Fokina and ninth seed Hubert Hurkacz in the second round. 

Two players who shared a birthday Monday also prevailed on their big day. 

On the day he turned 20, 11th seed Jannik Sinner defeated Federico Delbonis 6-2 7-5, while 10th seed Diego Schwartzman had to work a bit harder on his 28th birthday to down Daneil Evans 6-2 4-6 6-3. 

Elsewhere, 12th seed Felix Auger-Aliassime beat Marton Fucsovics 7-6 (7-0) 6-3, while 14th seed Alex de Minaur rallied to down Filip Krajinovic 0-6 6-4 6-4. 

Fifteenth seed David Goffin fell 6-3 6-3 to Guido Pella in the only seeded upset of the day. 

Other winners Monday included Karen Khachanov, Fabio Fognini, Lloyd Harris, Dominik Koepfer, Benoit Paire, Albert Ramos Vinolas and Mackenzie McDonald. 

Among those set to play their opening matches Tuesday are third seed Alexander Zverev, who will face Harris, and sixth seed Denis Shapovalov, who plays Paire. 

Daniil Medvedev lived up to his top-seed billing by overcoming Reilly Opelka in straight sets in the National Bank Open final.

World number two Medvedev prevailed 6-4 6-3 in Toronto on Sunday as he became the first Russian to win the ATP tournament since Marat Safin in 2000.

Medvedev now holds four of the nine ATP Masters 1000 titles, having also previously come out on top in Cincinnati, Shanghai and Paris.

He saved all four break points faced against unseeded Opelka, who stunned Stefanos Tsitsipas in the semi-finals, and needed just 85 minutes to complete the job.

Reflecting on his latest tour triumph, Medvedev said: "I could not have dreamt of this at one point.

"With Novak [Djokovic] and Rafael [Nadal] playing, it seemed like an untouchable achievement. Now I have four wins in five finals, which is a good score. I am just happy. 

"Playing Canada and Cincinnati, the goal is to win as many matches as possible. I was able to do it two years ago and I will try and do it again."

Opelka was competing in his maiden final at this level and started strongly, racing 40-0 ahead in the fourth game with some powerful hitting.

However, the 23-year-old – the first American to reach the final since Mardy Fish in 2011 – could not break his opponent as Medvedev recovered with some impressive serving to take the game.

Medvedev earned the first break in the following game and comfortably held to take the first set.

The Russian forced Opelka into errors in the second set and reeled off nine points in a row en route to breaking his opponent in the third game.

It was plain sailing from that point on as two-time beaten grand slam finalist Medvedev eased over the line to add another trophy to his collection.

Roger Federer will not take part in the upcoming US Open after the 20-time grand slam winner announced he is to undergo knee surgery that will rule him out for "many months".

The 40-year-old has not been in action since losing to Hubert Hurkacz in a Wimbledon quarter-final in July and has completed only five events this year.

Federer underwent two operations on his right knee in 2020 and requires another procedure that the legendary Swiss hopes will give him a chance to return to the court.

"I just wanted to give you a bit of an update on what's been going on since Wimbledon," Federer, who won the most recent of his five titles at Flushing Meadows in 2008, posted in a video message on his Instagram page on Sunday.

"As you can imagine, it's not been simple. I've been doing a lot of checks with the doctors as well on my knee, getting all the information as I hurt myself further during the grass-court season and Wimbledon.

"That's just not the way to go forward, so unfortunately they told me for the medium to long term to feel better, I will need surgery. I decided to do it.

"I'll be on crutches for many weeks and also out of the game for many months, so it's going to be difficult of course in some ways.

"But at the same time I know it's the right thing to do because I want to be healthy, I want to be running around later as well again and I want to give myself a glimmer of hope to return to the tour in some shape or form."

Federer, now ranked number nine in the world, missed more than a year of action after first having his knee operated on shortly after the 2020 Australian Open.

"I am realistic, don't get me wrong," he said. "I know how difficult it is at this age right now to do another surgery and try it. 

"But I want to be healthy, I will go through the rehab process I think also with a goal while I'm still active, which I think is going to help me during this long period of time."

Federer added: "Also a big thank you already now for all of your messages that are going to be coming in because you guys are always incredible. 

"You always think of me. Some of you suffer with me. I'll update you as I move along with my rehab. I wish you all the best and I'll check in with you soon."

The US Open in New York begins on August 30, with Dominic Thiem looking to retain his title.

Top seed Daniil Medvedev will face Reilly Opelka in the National Bank Open final after the American stunned Stefanos Tsitsipas in a three-set classic in Saturday's semi-finals.

World number 32 Opelka fought back from a set down in Toronto to knock out favoured third seed Tsitsipas in two hours and 32 minutes.

The 23-year-old American triumphed 6-7 (2-7) 7-6 (7-4) 6-4, booking a spot in his first ATP Masters 1000 final.

Opelka sent down 17 aces but also hit 27 groundstroke winners in the shock victory over 2021 Australian Open semi-finalist Tsitsipas who had beaten in-form Casper Ruud in the quarters.

"I played great," Opelka said in his on-court interview. “These courts suit my game, it is no coincidence that John Isner is in the other semi-final.

"Stefanos has definitely improved his returning. Come 5-5 in the first set, a lot of balls started to come back. He is a thinker and has a high tennis IQ, so it was expected, but that is what separates him from the rest of the pack."

Opelka was aided by an excellent first serve percentage of 72 per cent, winning 62 of 81 points when he made his first serve.

Both first two sets went to tiebreaks, with Tsitsipas failing to generate a break point until the third set. Opelka made the first break of the match in the seventh game of the third set and held serve twice after to seal victory.

World number two Medvedev cruised into the decider with a commanding win over John Isner in less than an hour.

Medvedev, who was runner-up in Toronto in 2019, won 6-2 6-2 over the big-serving American, with the match totaling 54 minutes.

Isner could only manage four trademark aces for the match, while the Russian had 11 and broke the American four times from seven opportunities.

Roger Federer "is a little uncertain" when he will be back in action just over a fortnight before the US Open gets under way.

The 20-time grand slam winner withdrew from both the Canadian Open and Cincinnati Masters this month as he continues to recover from a knee injury.

Federer has not played since losing to Hubert Hurkacz.in a Wimbledon quarter-final in July and has completed only five events this year.

The legendary Swiss, who underwent two operations on his right knee last year, is unsure if he will feature at Flushing Meadows.

He told Swiss newspaper Blick: "I haven't done anything for a long time because of my knee. After Wimbledon, I had to let everything sink in first.

"This week I'll meet my doctors and my team and then we'll see what happens next. At the moment everything is still a little uncertain."

Federer, who celebrated his 40th birthday last Sunday, remains upbeat despite such uncertainty.

He said: "You have to adapt. It has always been like this in my career. Factors change: degree of awareness, successes, experiences, identity and now just that.

"I'm a quiet guy who takes things with a sense of humour. I always see the good in every situation. If it's not good right now, I know it will get better and it could be a lot worse.

"I am doing very well. My family is healthy. I just turned 40 and I'm still active. Who would have thought it? Certainly not me. I am totally at peace with myself and I am sure that there will be a lot more beautiful things to come."

Novak Djokovic drew level with Federer and Rafael Nadal on 20 major singles titles by winning Wimbledon and the world number one will be bidding to complete a calendar Grand Slam in New York.

Casper Ruud continued his excellent winning streak while Stefanos Tsitsipas made it a birthday to remember at the National Bank Open in Toronto.

Tsitsipas turned 23 on Thursday and marked the occasion with a 6-3 6-2 win over Karen Khachanov.

The Greek star was presented with a cake by tournament officials after his win, as the crowd serenaded him with a chant of 'happy birthday'.

It marks a significant improvement on when Tsitsipas turned 20. On that occasion, he lost the 2018 final of this event to Rafael Nadal.

Next up for Tsitsipas is Casper Ruud, who poked fun at his critics after he eased into the quarter-finals.

Ruud, the world number 12, won three titles on clay courts in July and has now continued that form in the ATP Masters 1000 event.

Playing on a hard court has proved no challenge for the in-form Norwegian, who wrote 'Hard Courts' with a smile underneath on the camera after his 6-4 6-3 victory over Dusan Lajovic on Thursday.

"I have seen a lot of people questioning my ability to play on hard court, so I just thought it was funny to write a little note," Ruud said in a news conference.

"I think it's fun to play on hard courts. Even though I (have achieved) most of my best results on clay, my best slam result is from this year’s Australian Open (where he reached the Round of 16), so I think it's a surface that also can suit my game well even though this year has been mainly clay.

“I think I'm motivated to come back to the hard courts. I have had two very good matches here. It's a great start for me to the hard-court swing."

Ruud, in the hunt for his fifth title of 2021, has won the only previous meeting between the duo.

"[I am] looking forward to that battle," Tsitsipas said. "We have played each other in the past. Not an easy guy to play against. Looking for a change, looking for a switch-up this time."

However, there was no place in the last eight for world number seven - and Olympic gold medallist - Andrey Rublev, who went down 7-5 7-6 (7-5) to American John Isner.

Fresh from a triumph in Atlanta, 36-year-old Isner has looked sharp all week and has now won eight successive matches.

It brings up a third quarter-final appearance for the world number 30 in Canada, and he will play French 11th seed Gael Monfils after he got past lucky loser Francis Tiafoe 6-1 7-6 (7-2). Monfils will be competing in his first ATP Tour quarter-final in 18 months.

Top seed Daniil Medvedev proved too good for Australian qualifier James Duckworth, winning 6-2 6-4 in one hour and eight minutes.

Medvedev was in ominous form on the hard court, sending down 10-1 aces and winning 27 of 32 points on his first serve.

The Russian world number two will play seventh seed Hubert Hurkacz who fought back to win 6-7 (7-9) 6-4 6-4 over Nicolas Basilashvili.

Eighth seed Diego Schwartzman lost in three sets to 10th seed Roberto Bautista Agut after the Spaniard saved three match points.

Bautista Agut will next play Reilly Opelka who came from behind, and also saved a match point, to win over Lloyd Harris in three.

Canadian fifth seed Denis Shapovalov was a major casualty in the second round of the National Bank Open in Toronto after a straight-sets defeat to Francis Tiafoe.

Unseeded American Tiafoe swept aside the local 6-1 6-4 in one hour and 15 minutes to secure his third-round spot against 11th seed Gael Monfils who beat John Millman 3-6 6-3 6-4.

Tiafoe was only in the Toronto main draw as a lucky loser after being defeated in qualifying by Emil Ruusuvuori but he hit 14 winners in an emphatic display.

World number 10 Shapovalov was unable to generate any break points while Tiafoe reeled off five games in a row, with two breaks, to win the first set.

The Canadian continued to struggle with his serve in windy conditions, as the American world number 52 won 88 per cent (23/26) of points on his first serve.

Another local hope, ninth seed Felix Auger-Aliassime, also was eliminated, going down 7-5 6-4 to Serbian Dusan Lajovic.

The Canadian hit six aces to Lajovic's none, but was undone by unforced errors at key times, with a double fault gifting the Serbian a 6-5 lead in the opening set.

Australian 12th seed Alex de Minaur also bowed out after a one-sided 6-1 6-1 defeat to Georgian world number 42 Nicolas Basilashvili.

Basilashvili sent down 6-2 aces and converted five of his six break points generated in an impressive display.

Australian qualifier Jack Duckworth booked a third-round ticket against top seed Daniil Medvedev after upsetting 16th seed Jannik Sinner, who won last week's Citi Open.

Fourth seed Andrey Rublev won through with a 7-6 (7-4) 6-3 victory over Fabio Fognini, while seventh seed Hubert Hurkacz progressed with a walkover after Kei Nishikori retired with a shoulder injury.

Eighth seed Diego Schwartzman beat Benoit Paire 7-5 6-1, while 10th seed Roberto Bautista Agut handled Tommy Paul 6-3 6-4.

John Isner knocked out 13th seed Cristian Garin in three sets, while Lloyd Harris beat Feliciano Lopez in two and Karen Khachanov defeated compatriot Aslan Karatsev 7-6 (9-7) 6-4 to secure a third-round meeting with third seed Stefanos Tsitsipas.

Tsitsipas pledged to help those affected by the fires in his homeland in his post-match press conference on Tuesday.

“My heart is with all the people of Greece,” Tsitsipas said. “I come from the south suburbs of Athens. When I was there a few days ago, I could see the fires from the south. Huge, giant clouds, smoke, which you could see from far, far away. It wasn't very nice. Even at the beach that day when I went to swim, you could see all the debris from the smoke and from the fires in the sea.”

Daniil Medvedev and Stefanos Tsitsipas survived three-set scares at the National Bank Open on Tuesday, but five-time tournament champion Rafael Nadal departed Toronto without even taking the court. 

Top seed Medvedev, who won just three games against Nadal in the final in 2019, the last time the tournament was played, prevailed 4-6 6-3 6-4 in his opener against Alexander Bublik.

The man Nadal beat to win the title the previous year, Tsitsipas, failed to convert on five match points in an epic second-set tiebreak but recovered to down Ugo Humbert 6-3 6-7 (13-15) 6-1.

Nadal pulled out ahead of a scheduled match against Lloyd Harris, who beat him last week in Washington as the 20-time grand slam winner struggled with a foot injury. 

Countryman Feliciano Lopez replaces Nadal in the draw and will face Harris on Wednesday. 

Elsewhere Tuesday, sixth seed Casper Ruud needed more than two hours to put away Marin Cilic 6-3 3-6 6-3, while 14th seed Grigor Dimitrov suffered a quick 6-3 6-4 exit against big-serving American Reilly Opelka.

A pair of unseeded veterans advanced, with 2016 finalist Kei Nishikori a 6-4 6-7 (5-7) 6-2 winner over Miomir Kecmanovic and John Isner defeating Alejandro Davidovich Fokini 6-4 6-1 in just over an hour.

Two days after appearing in his first ATP Tour final at the Citi Open, Mackenzie McDonald fell 6-3 6-4 to Benoit Paire in his Toronto opener. 

In other first-round matches, Karen Khachanov beat Cameron Norrie 6-4 5-7 6-4, Frances Tiafoe downed Yoshihito Nishioka 6-4 6-3, Dusan Lajovic handled Emil Ruusuvuori 3-6 6-3 6-3 and Nikoloz Basilashvili defeated Jenson Brooksby 2-6 6-0 6-4.

Rafael Nadal has withdrawn from the National Bank Open ahead of his opening match due to a left foot injury.

The Spaniard made a return to action on the ATP Tour last week at the Citi Open, his first outing since suffering defeat to Novak Djokovic in the semi-finals of the French Open in June.

His comeback was aimed at getting prepared for the US Open but, having lost in the last 16 in Washington to Lloyd Harris, he will not now be participating in Toronto.

"I really wanted to play here a lot, but now is the moment to make a decision, and this is unfortunately the decision that I have taken," Nadal told the media.

"I have had this issue for a couple of months, as people know.

"Of course, it is not a happy situation after all the success that I had here in Canada, not being able to play this year after missing a year. It's a tough one, but that's how it is today."

Nadal skipped Wimbledon citing the need to recover after the clay season, while the left-hander also opted out of representing his country at the Tokyo Olympics.

The five-time champion in Toronto was scheduled for a repeat meeting with Harris in the second round. Instead, his place in the draw goes to compatriot Feliciano Lopez.

South African Lloyd Harris booked a second-round date with Rafael Nadal at the National Bank Open after a straight-sets win over Canadian qualifier Brayden Schnur on Monday.

World number 49 Harris eased past Ontario-born Schnur 6-3 6-2 in one hour and 17 minutes in Toronto.

Harris sent down nine aces, winning 78 per cent of points on his first serve, converting four from four break points on return.

Nadal is a five-time champion in Toronto, winning the previous two editions in 2018 and 2019.

Marin Cilic, who won his first title for three years in Stuttgart, beat Albert Ramos-Vinolas 6-2 4-6 6-3 in two hours and 13 minutes.

The 32-year-old will face sixth seed Casper Ruud in the next round.

Fabio Fognini also needed three sets to progress, battling from behind to defeat Jan-Lennard Struff 6-7 (2-7) 6-2 6-4 to set up a meeting with Andrey Rublev.

Ugo Humbert impressed in his straight-sets defeat of Lorenzo Sonego and will next face third seed Stefanos Tsitsipas, while qualifier James Duckworth beat Taylor Fritz to secure a showdown with Citi Open winner Jannik Sinner.

Alexander Bublik defeated Briton Dan Evans in straight sets to earn a second round meeting with top seed Daniil Medvedev, while Australian John Millman will face 11th seed Gael Monfils after beating Ricardas Berankis.

Reilly Opelka came from a set down to win over Australian Nick Kyrgios, while Tommy Paul also fought back to beat Canadian Vasek Pospisil.

Novak Djokovic will not play at the Western and Southern Open after a "taxing" run that has brought him to the brink of a calendar Grand Slam.

The world number one's bid for a Golden Slam faltered at the Olympic Games as he lost to Alexander Zverev in the semi-finals in Tokyo.

Djokovic appeared to tire badly and finished fourth in both the men's singles event and the mixed doubles, opting out of the bronze medal match in the latter.

But victories at the Australian Open, French Open and Wimbledon mean 2021 is still on course to be the best year of Djokovic's career.

And the Serbian is taking a little time to prepare himself for the final push at Flushing Meadows, meaning no appearance in Cincinnati next week.

"Dear fans," he wrote on Twitter. "I wanted to share with you that I am taking a bit longer to recover and recuperate after quite a taxing journey from Australia to Tokyo.

"Sadly, that means I won’t be ready to compete in Cincinnati this year, so I'll turn my focus and attention to the US Open and spend some more time with family.

"See you in New York soon!"