Nadal's stamina and famous fitness have been put to the test on the sweltering Flushing Meadows hardcourts as he has logged almost 16 hours through five matches.
Nadal said that he first felt a knee problem in his second- or third-round match last week and that it acted up again Friday starting in the fifth game.
The US Open men's semi-finals take place tonight in NY, and returning to preview the two matches, is our tennis columnist, Dan Weston.
"I hate retiring but to stay one more set out there playing like that is too much for me", said Nadal.
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Nadal, the world's No. 1 player and the defending champion in NY, retired against Juan Martin del Potro, trailing 7-6 (7-3), 6-2 about two hours into the first semifinal of the day in Flushing Meadows. After losing the first three matches of his comeback this year, he has gone on to reach the quarter-finals at Roland Garros, lose to Nadal in the semi-finals in Rome and in the Queen's final to Cilic, before beating Kevin Anderson in the Wimbledon final. I going to keep fighting and working hard to keep enjoying this tour and keep having chances to compete at the highest level.
It's the eighth time the Serb will have been in the final in NY, though he has only lifted the trophy twice before.
After failing to make much attempt to reach a dropshot he summoned the physio and took a medical timeout at 2-1 down in the second.
Djokovic, the victor in 2011 and 2015, faces Kei Nishikori in Friday's semi-finals, his 11th successive appearance in the last-four. He was visited by a trainer at the changeover after the match's seventh game and tape was applied below the joint.
Nadal came through an enthralling five-set quarter final with Dominic Thiem in which he lost the first set 0-6 before rallying to clinch the match on a tie-break in the deciding set. Certainly, the market has made a big adjustment on predicted pricing, and I'm not at all convinced that it should do to this extent.
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Having fought through his own injury-ravaged years, Del Potro understood his opponent's pain and gave him a warm embrace before he left the court. "But at some point you have to take a decision", Nadal told reporters.
Djokovic's most recent win over him was in the quarter-finals at Wimbledon this summer, on his way to winning the title.
He will have a shot at the hat-trick on Sunday, though, when he comes up against 2009 champion Del Potro.
Nadal was able to feel at least some pleasure for Del Potro after all his struggles: 'He's a player that went through lot of issues during his career, like me too.
One of the greatest players of all time, the one chink in the Spaniard's armour has always been his knees with injuries plaguing him throughout his career. In the final when I beat Rafa and then Roger I was a kid then, but now I am much older'.
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