Juan Martin del Potro has reached the semi-finals for the third time in the past five grand slams after coming through a gruelling US Open quarter-final battle with John Isner.

The two big men battered each other to near exhaustion in the heat and humidity in Arthur Ashe Stadium but it was the Argentine third seed who proved the stronger in a 6-7 (5-7) 6-3 7-6 (7-4) 6-2 victory that lasted three-and-a-half hours.

With the mercury hitting 32C and and humidity at about 50 per cent, the US Tennis Association invoked its new extreme heat policy, which allowed the players to take a 10-minute break after the third set, but that clearly didn’t help Isner, who quickly trailed 3-0 in the fourth.

“I’m so happy to reach another semi-finals in my favourite tournament,” the 2009 champion said in his on-court interview.

“That’s very special to me. Beating John in these kind of matches is like an epic, an epic match.”

Del Potro’s serve held up at crunch moments and he saved the three break points he faced while he managed the break Isner on three occasions, including the final game of the match.

Isner hit 67 winners to Del Potro’s 49 but the victor made just 14 unforced errors to prove too consistent for his good friend.

Del Potro will face top-ranked Rafael Nadal or ninth-seed Dominic Thiem for a place in Sunday’s title decider.

Nadal beat del Potro last year in the last four at Flushing Meadows, and again this year in the semi-finals of the French Open.

Isner was trying to become the first American man to reach the US Open semis since Andy Roddick in 2006.