Rafael Nadal qualified for the US Open quarterfinals after beating Alexander Dolgopolov 6-2 6-4 6-1 and was joined by Rodger Federer who dismissed Philipp Kohlschreiber 6-4 6-2 7-5.
Juan Martin del Potro however took center stage coming from two sets down and saving two match points in the 4th set before beating sixth seed Dominic Thiem 1-6 2-6 6-1 7-6 (7-1) 6-4.
Despite feeling ill and requiring treatment, Del Potro came through in three hours and 35 minutes to set up a tantalizing quarter-final against Federer.
Federer 36, struggled with a back injury in the build-up to the tournament and left the court after the second set for a medical timeout.
“I just needed a bit of a rub on my back, I just didn’t want Philipp to wait. It was more precaution. It’s all good. No problems there. I’m not worried about it. I’m sorry I had to do it.”
Russian teenager Andrey Rublev set up a quarter-final clash with Nadal after knocking out Belgian ninth seed David Goffin.
Rublev, 19, won 7-5 7-6 (7-5) 6-3 to become the youngest man to reach the last eight at Flushing Meadows since Andy Roddick in 2001.
“I’m a little bit lucky to be in the quarter-final but of course I’m enjoying it, and I will try to do my best in the next match,” said Rublev.
“Rafa is the real champion and I’m just going to try to enjoy it – this is the quarter-final and I have nothing to lose.”
Nadal returns to the last eight for the first time in four years after overcoming several injury setbacks for the last two years.
In the women singles Venus Williams booked her place in the US Open quarter-finals with a three-set victory over Carla Suarez Navarro.
And will now face Petra Kvitova after the Czech 13th seed beat Garbine Muguruza.
“The energy of the crowd here, it makes me feel I’ve got to hit a winner, I’ve got to hit an ace. I love it here,” Williams said in front of the Arthur Ashe Stadium crowd.
Williams has now progressed from the last 16 at Flushing Meadows 12 times since making her debut in 1997.
Madison Keys made it four American women in the US Open quarter-finals with victory over fourth seed Elina Svitolina.
Keys, seeded 15th, won 7-6 (7-2) 1-6 6-4, ending Svitolina’s hopes of becoming world number one.
The Ukrainian needed to at least reach the semi-finals to have a chance of topping the rankings.