Novak Djokovic’s U.S. Open withdrawal through injury has sent shockwaves through the tennis betting markets.

Djokovic was the defending champion and No. 1 seed in New York as he sought a 17th Grand Slam title.

He was the heavy favorite to claim the crown and maintain his stellar 2019 season, which has already seen the Serb victorious at the Australian Open and Wimbledon.

But his decision to withdraw injured midway through his fourth-round clash with Stan Wawrinka has caused a dramatic shift in U.S. Open tennis betting odds.

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Rafael Nadal has suddenly become the title favorite, while Djokovic’s projected opponents in the quarter and semifinals have all received a boost.

Here, we take a look three best bets you can now make following Djokovic’s shock withdrawal.

All Eyes On Rafael Nadal

Of course, once Djokovic announced his exit from the U.S. Open the attention turned towards Nadal. The Spaniard is targeting a 19th Grand Slam title and a second of the season following his usual success at Roland Garros. Nadal was +220 with William Hill to win the U.S. Open before Djokovic’s exit. That price has already crashed to -125 as he prepares to take on Diego Schwartzman in the quarterfinals.

Is a first time Fedal match-up at the #USOpen on the cards...?https://t.co/AhfMZWryJN pic.twitter.com/mgpIk9OoYP

— US Open Tennis (@usopen) September 3, 2019

It is easy to understand why Nadal’s price has collapsed into the negatives. After all, he is a seasoned winner in New York. But crucially Nadal has also kept away from injuries over the summer months — something he is suspect to suffering in post-French Open tournaments each season.

There is no sense that Nadal is injured or carrying anything major at this point of the tournament — and that should scare his rivals.

As far as the tennis is concerned, Nadal has a 7-0 record over quarterfinal opponent Schwartzman and is projected to meet either Gael Monfils or Matteo Berrettini in the semis. Monfils has managed just two wins over Nadal in 17 attempts (the last of which came in 2012) and Berrettini has never faced the Spaniard.

Hearts Flutter For Federer

Roger Federer is still going strong at the age of 38 and is desperate to add to his Grand Slam haul of 20. The Swiss maestro reached the final of Wimbledon earlier this summer but could not get past Djokovic in a thrilling encounter.

Federer dropped sets in his opening two matches here in Flushing Meadows but then cruised past Daniel Evans and David Goffin with ease. He faces the unseeded Grigor Dimitrov in the quarterfinals and this is a tricky prospect for the veteran star.

Remember, Dimitrov was once tipped as the ‘next Roger Federer’ and it’s only been over the past 18 months that his career has taken a dive. Now aged 28, it is remarkable a player of Dimitrov’s talent has only twice made it to a Grand Slam semifinal.

One-handed backhand lovers, this match up is for you ?#USOpen pic.twitter.com/n7Xuixx0zN

— US Open Tennis (@usopen) September 3, 2019

Dimitrov has dropped just one set so far in New York, although he did benefit from Borna Coric’s withdrawal in the second round. The Bulgarian is not expected to get past Federer but could push the Swiss into five sets here.

For many tennis betting fans, the desire to see Federer lift another Grand Slam title is strong. And they have backed the Swiss into second-favorite behind Nadal. Federer is +200 with 888 Sport to claim the title, having been out at +600 before Djokovic’s withdrawal.

Now the threat of meeting Djokovic in the semifinals is over, fans are starting to gravitate towards Federer.

Wawrinka ahead of Medvedev

Daniil Medvedev was the fourth favorite to win the U.S. Open — behind the Big Three of Djokovic, Federer, and Nadal — before the tournament started. That was largely down to his Cincinnati Masters triumph earlier in the summer that catapulted the Russian into the spotlight.

But while Medvedev is still in contention here, his performances in New York have been worrying. The fans have begun booing the 23-year-old, who has been taken to four sets in each of his last three matches. There is a sense that Medvedev — priced at +1200 to win the U.S. Open — is running out of steam.

Check out today's featured day match: Stan Wawrinka (SUI) vs. Daniil Medvedev (RUS) https://t.co/Q88Ts56BNb pic.twitter.com/gcueYH8XkL

— US Open Tennis (@usopen) September 3, 2019

And that’s why the surprise name of Stan Wawrinka has now peaked in the betting markets. The Swiss won the U.S. Open back in 2016 but was not expected to impress this year, with his career regarded as being in decline.

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RELATED: Why Daniil Medvedev Is A Great Value Bet To Win The U.S. Open

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Yet Wawrinka was dominating Djokovic when the latter quit their fourth-round match and has grown into this tournament. His odds have tumbled from +4000 at the start of the tournament to just +900 now.

Wawrinka and Medvedev meet in the quarterfinals in what is certainly the match of the round. The winner will likely play Federer in the semis.