Nadal, who had never before retired from a U.S. Open match, showed signs of distress nearly from the start as he limped noticeably after a grueling 69-minute opening set.
"Of course, it's not the best way to win a match", said del Potro, who hugged Nadal when it was over.
After having his right knee taped, Nadal threw in a sloppy game to be broken again at 4-4, giving Del Potro the chance to serve out the opener.
Nadal, a 17-time Grand Slam champion, mentioned retirement to the chair umpire midway through the second set, then threw in the towel after dropping the set.
This was the sixth win for the Argentinian over the 17-time Grand Slam champion and the second in best-of-five matches after that triumph in NY nine years ago. "I love to play with Rafa because he's the biggest fighter in this sport".
When Rafael Nadal finally finished a almost five-hour climb into the U.S. Open semifinals, he thought backward as much as ahead. That includes a four-set victory in the Wimbledon quarter-finals, where Djokovic burst out of his malaise to win make his first title in more than a year his 13th Grand Slam crown. 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.
I am having a lot of success. "I don't like to see him suffering on court today".
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Defense Secretary Jim Mattis, U.N. ambassador Nikki Haley and Treasury Secretary Steve Mnuchin also issued denials. CNN reports that they received an advance copy of Woodward's book, which included a reproduction of the letter.
Djokovic's most recent win over him was in the quarter-finals at Wimbledon this summer, on his way to winning the title. "I don't know. I would give slight advantage to Rafa, but I feel it's going to be a great match".
Nadal said: "I think it was 2-2 in the first, 15-0, that I felt it".
But he took a medical time-out after three games of the second set and, as he limped around the court, it became increasingly clear that he was in serious trouble. He even barely took any time between points while serving - and he's known as one of the slowest guys on tour. "I know how much frustration (there) can be when you can't do the thing that you want to do", Nadal said.
"It's not a match when one is playing and the other is at the side of the court", Nadal added.
"I can not compare the knee with other times because the pain on the knee is always very similar", he said. This is my favourite tournament, my biggest memories on a tennis court came on this court in 2009.
Del Potro, who has also had his career disrupted by injuries, was not happy to get the victory the way he did but the big-hitting Argentine will now get a chance to raise a Grand Slam trophy nine years after his first.
Del Potro sensed blood and broke for 3-1 as Nadal struggled for movement.