On Sunday, the powerful Argentine with the massive forehand that zips along at more than 100 miles per hour (160 kph) will face two-time U.S. Open champion Novak Djokovic or 2014 runner-up Kei Nishikori. The two that preceded the Wimbledon classic were easier victories, a semifinal rout en route to the French Open title and a four-set victory in last year's U.S. Open semifinals, when Nadal dominated the last three sets.
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. I have tremendous respect for him as a person and a player. I feel that this is largely due to these fitness concerns, but the lengthy rest period for Nadal is likely to be of great benefit.
Many experts have long felt Nadal's physical style of play, which relies on power and athleticism in contrast to his more graceful rival Roger Federer, puts him more at risk of injury. It was so hard for me to keep playing, I was in too much pain.
In Wednesday's other quarter-final, Marin Cilic was ousted in five sets by Kei Nishikori, despite winning more points in the match and creating four more break point chances - such are the fine margins often required to win tennis matches.
"That was not a tennis match at the end".
Coming into this semi-final, he had already spent nearly 16 hours on court.
Nadal suffered problems with his right knee during his third-round win over Russian Karen Khachanov but insisted it was not a major issue and subsequently won gruelling matches against Nikoloz Basilashvili and Dominic Thiem.
The effort took its toll, with the Spaniard twice needing to have his right knee bandaged before calling it a day after the conclusion of the second set.
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"It is not the best way to win a match".
"You could imagine it was very hard for me to say goodbye before the match finishes", said Nadal, who added that he had been dealing with his knee woes since the early rounds.
Nadal's challenge looked doomed even as early as the first set, as he was feeling the injury after just four games, he admitted.
Del Potro led a standing ovation on Arthur Ashe Stadium when Nadal walked gingerly off court.
But the big Argentine swept through the tiebreaker, wrapping up the opener after 69 minutes of impressive shot-making.
STATISTICAL BREAKDOWN Del Potro  bt Nadal  7-6 [7-3] 6-2 Ret.
"It's not the best way to win a match", said Del Potro. I didn't expect to get in another grand slam final. "I love to play against Rafa because he is the biggest fighter in the sport", Del Potro said. "I was a kid then and now I'm much older". It was plain sailing for the 31-year-old Serb who is chasing a 14th Slam title to take him level with Pete Sampras on the all-time list.
That didn't stop him losing the set, though, and he was forced to save five more break points at the beginning of the second in a 14-minute game.