Nishikori improved in the second set, coming to the net more often, but Djokovic was in imperious form.
Nadal attempted to hold his serve down 2-5 in the second but was broken to drop the set. You could imagine very hard for me to say good-bye before the match finish.
The third seed could not take the opportunity as two set points went begging, but Nadal - who swiftly removed the tape from his knee - nevertheless found himself behind in another match as his rival's forehand strength came to the fore in a tie-break. I know that I will have to play at my highest level to keep having chances of success.
As he shook hands with the umpire and a typically gracious and sensitive Del Potro, Nadal struggled to contain his emotions.
Perhaps it's because del Potro was sandbagging. "But I think that is completely in the past, and now I'm having a good present, looking forward for the future".
The Spaniard, who was famously was one of Del Potro's victims when he won his only Grand Slam title in 2009, expects another high-octane clash.
It was the second time this year that the world number one has retired from a slam as he also quit during his quarter-final against Marin Cilic at the Australian Open in January. The match lasted almost five hours, did not finish until Wednesday morning, and was the longest of Nadal's US Open career. Tendonitis has dogged him.
"I didn't know if I will be a tennis player again or not", Del Potro said Friday. Was not something progressive. "I got depressed for a couple of months also". Is not an injury that tells you three weeks off and you are back. "But I don't know".
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Of the now nine grand slams he has played since returning, Del Potro has reached the quarter-finals twice, the semi-finals twice and, at last, another final, where he awaits the victor of Novak Djokovic's clash with Kei Nishikori. "Last year was a fantastic year".
He is 45-4 this season, with half the losses due to injury retirements. I am playing well.
"It means the world to me obviously", he added.
"I think that's very important".
"All my career everybody say that because of my style, I will have a short career", said Nadal.
Del Potro will now face Djokovic, the 2011 and 2015 victor, who reached his eighth final at the tournament and 23rd of his Grand Slam career with a 6-3, 6-4, 6-2 stroll past Japan's Kei Nishikori.
Should he win, Djokovic will become just the second man in the Open Era - after Roger Federer - to win three or more titles at three separate Grand Slam events, while he will match Pete Sampras' haul of 14 major titles - moving within three titles of Rafael Nadal in the all-time list. On the other side of the net Djokovic will be facing Juan Martin Del Potro who has an even more heartening comeback story. This is my favourite tournament, my biggest memories on a tennis court came on this court in 2009.
"I waited as much as I can", he said. "But it definitely makes me realize that, OK, I can definitely do my best if he can, too".
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