The 17-time Grand Slam champion clinched victory when Thiem hit an overhead smash long on the first match point, the drama continuing until the last shot in an epic encounter lasting four hours and 49 minutes. At Wimbledon, Nadal came back from two sets to one down to win in five in a quarter-final which stretched to nearly five hours.
Earlier the 36-year-old Williams, who is bidding for a record seventh title at Flushing Meadows as well her 24th major singles crown, started sluggishly in the night session, allowing Pliskova to take a 3-1 lead in the opening set before rebounding to win 6-4, 6-3. On Monday night, Roger Federer fell to unseeded John Millman, ending the world No. 2's dreams of capturing a title he hasn't won in a decade. "I was having a baby this time a year ago so I have nothing to prove". After that first set, then the match became more normal.
"He's a close friend on tour, a great guy and I wish him the very best. he is young and has plenty of time to win tournaments".
The two players combined for 129 winners-74 for Thiem, 55 for Nadal-and Thiem actually won six more points overall than Nadal did.
Nadal trailed by a break in the third set before taking it.
The Austrian was heartbroken but proud, saying: "It's going to be stuck in my mind forever". I am focused on try to make that happen.
The Spaniard saved a break point in games nine and 11 but he stood no chance in the tie break, losing it 7-4 following a routine forehand that he sent into the net, handing the set to his rival and setting up a decider after more than three and a half hours of wonderful battle! "I hope that we have many more in the future with a different end".
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"It's been a great battle, the conditions were tough, a lot of humidity". "Forever I'm going to remember this match, for sure".
He said: "I have my trophy at home".
After suffering a first set "bagel", Nadal had to battle back from breaks in the third and fourth sets before seeing off the first top 20 player he had faced at the US Open since 2013. But once again Nadal stepped up the level, saved two break points in the game and then went on to claw back to 4-4. And I played against a great opponent. It's cruel sometimes tennis, because I think this match didn't really deserve a loser.
His victory against the world number one in the Madrid semi-finals ended Nadal´s 50-set clay win streak which began after the Austrian had beaten him in Rome 12 months earlier.
Despite that, the 29-year-old was never broken in the 3 hour 31 minute match where Isner unleashed 26 aces but was undone by 52 unforced errors compared to Del Potro's 14.
Nadal has played a total of 15 hours, 54 minutes through five matches here.
Nadal seemed to be on the verge of cracking the code when he broke back in the fourth and came within two points of winning the match.