Nadal had had his right knee taped during his gruelling third-round clash against Karen Khachanov but insisted afterwards it was not a big issue and he appeared in good shape for his next two matches.
The world number one had spent more almost 16 hours on court in reaching the last four, averaging more than four hours a match during the last three rounds, and that took its toll here.
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.
Rafael Nadal of Spain reacts during his men´s singles semi-final match against Juan Martin del Potro of Argentina on Day Twelve of the 2018 US Open at the USTA Billie Jean King National Tennis Center on September 7, 2018. "But it was not a tennis match at the end. Just one player playing, the other staying on one side of the court", Nadal said.
Del Potro now awaits the result of Novac Djokovic's match against Kei Nishikori to find out his opponent in the final, following the 7-6 (3), 6-2 injury win.
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"I waited as much as I can", said Nadal. He pulled out during an Australian Open quarterfinal with an upper right leg injury against Marin Cilic in January.
"It was hard for me to keep playing".
Following these, Nishikori and Djokovic meet in the second men's semi-final tonight, which will start not before 2300 United Kingdom time, although in all likelihood, quite a bit later. Lot of people in this room, including myself, would never have thought that at the age of 32 I will be here fighting for titles, fighting for the first positions of the rankings.
Nadal recovered in typically gutsy fashion, but took a medical timeout at the end of the game for more treatment and it soon became clear he was in major trouble.
Meanwhile, sixth-seeded Novak Djokovic reached his eighth U.S Open final, defeating Kei Nishikori 6-3, 6-4, 6-2 on Friday.
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In these, Nadal eliminated Del Potro at this stage last year here - priced much shorter at [1.36], before eliminating him in this year's French Open and Wimbledon - again priced considerably shorter than market lines.
Djokovic missed last year's tournament owing to an elbow injury.
"From my experience, and I can only talk about myself, this has been definitely the toughest US Open in the last ten years that I have played in in terms of conditions", said the 13-time major victor.
It's the 10th time del Potro has beaten the No. 1 player, so this isn't new ground for him.
While Djokovic has been able to routinely beat Nishikori in their previous meetings, Nadal and Del Potro have only met on four occasions since 2013.
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I have had three surgeries and every time I had extreme doubts over whether I would get back. "I have prayed for that". Elsewhere in the men's bracket, No. 7 seed Marin Cilic moves on to meet No. 21 seed Kei Nishikori in a quarterfinal.
He will have a shot at the hat-trick on Sunday, though, when he comes up against 2009 champion Del Potro. This is my favourite tournament, my biggest memories on a tennis court came on this court in 2009.