Third seed Del Potro, the champion in 2009, was 7-6 (7/3), 6-2 ahead when Nadal retired.
And they have emerged as towering forces at this tournament.
Mike Bryan broke a tie for most major doubles titles with John Newcombe, and at 40 years, 4 months became the oldest Grand Slam doubles champion in the professional era. Pain in his wrists prevented him from defending his title in 2010, then worsened to the point where he spent more time in the company of surgeons than his rivals on the Tour. But fate had other plans. When I played Roger nine years ago, he was the favorite to win as well.
Given that I've already sided heavily with Del Potro pre-tournament, I won't be looking to increase my exposure here, but I wouldn't discourage anyone from supporting him to win 3-2 at around [9.00]: he's already beaten Nadal and Federer on the hard courts this year and can complete his triumvirate scalping here.
When Del Potro takes the court on Sunday he will look to not only end a nine-year Grand Slam title drought but also extend a comeback from when he nearly quit professional tennis three years ago. "If not, I've been playing a great tournament and I will be happy anyway".
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"I hate to retire, but stay one more set out there playing like this will be too much for me".
Victory over Juan Martin del Potro on Sunday will give him not only his 14th major title but also underline the Serbian is ready to reclaim his mantle as the top dog in the sport.
The boot was on the other foot on Saturday when he benefited from another player's injury, Rafael Nadal retiring with knee problems at two sets down.
Nadal hardly ever retires. The lights in Arthur Ashe Stadium were on for the start of Nadal vs. del Potro, and they engaged in some terrific shotmaking during the first set. Let's hope he is not out for too long. "I will be proud if I (am) still playing tennis for more years".
Nadal continued but, after Del Potro won the second set to lead 7-6 (7/3) 6-2, Nadal had one last chat with the trainer, shook his head and offered his hand to his opponent.
The first set advanced to the tiebreaker after Argentina's World No. 3 drew back at 6-6.
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He won his biggest career trophy, after the 2009 US Open, when he ended Federer's unbeaten streak at Indian Wells in March.
In his lengthy efforts to fully recover from his wrist injuries, del Potro almost gave up tennis in 2015. That might make him the hungrier player but a large contingent of Argentines is sure to make him the crowd favourite.
Widely considered the best returner in the game, he kept accumulating chances - and then failing to cash them in.
He has a ridiculously strong tennis tool chest. He played on but could hardly compete with the bludgeoning shots from the Argentine. Del Potro was sympathetic, but he could not hide a beaming smile.
"We didn't do anything special after the match", Nadal's coach, Carlos Moya, told ESPN.com on Thursday. You never know what could happen in the future.
Djokovic, bidding for his second straight major title, would seem to have the easier road to the final. "Even before I went through the whole process of surgery, post-surgery recovery, I was still feeling for players that went through injuries", Djokovic said.
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