In conditions that felt more like an oppressive 23,000-seat steam room than the largest tennis stadium in the world, John Isner's bid to make history came up short Tuesday.

The former Georgia Bulldog was attempting to become the first American man since Andy Roddick in 2006 to reach the U.S. Open semifinals, but instead No. 11 Isner succumbed to No. 3 Juan Martin del Potro, 6-7(5), 6-3, 7-6(4), 6-2 in the quarterfinals in Arthur Ashe Stadium. The match lasted 3 hours, 31 minutes.

The temperatures during the match reached the mid-90s, and despite having an open roof, Ashe Stadium felt like a sauna with no air circulation or ventilation. Like many players during this tournament, Isner wore an ice vest during changeovers. He changed his shirt 11 times because it was soaked with sweat. And at times during the second set, the 6-foot-10 Isner staggered on court because of the brutal heat.

“Yeah, it's tough conditions out there, no doubt,” Isner said. “It's very humid ... in that center court. (The) air is pretty still for whatever reason. Maybe it's the roof structure. It's pretty humid and takes its toll on us players.

“It definitely is tough conditions, but I wish I could have done a little bit better out there. It just wasn't to be. He's so good. It was a tough match.”

The 6-6 Del Potro, the 2009 U.S. Open champion, advanced to play the winner between defending champ and world No. 1 Rafael Nadal and No. 9 Dominic Thiem in the semifinals Friday. Nadal and Thiem were slated to meet Tuesday night in another quarterfinal.

“I'm so happy to reach another semifinals in my favorite tournament,” del Potro, who lost to Nadal in the semis a year ago, said in his on-court interview. “That's very special to me. And of course beating John in these kind of matches is like an epic match. We're both tired in the end. We both fight all the match and I think I survived with my serves in a couple of important moments of the match and that was the only key.”

Del Potro improved to 8-4 against Isner and has now won their past five encounters, all on hard courts.

Isner, 33, as also was bidding to make his second Grand Slam semifinal of the summer, having reached that round at Wimbledon before losing 26-24 to Kevin Anderson in the fifth set. It was the second-longest match in Wimbledon history, behind only Isner's match against Nicolas Mahut in 2010 that went to 70-68 in the fifth set.

Isner also captured his first Masters 1000 title in March in Miami, and then last month won the BB&T Atlanta Open for the fifth time in six years.

Of course, becoming the first American since Roddick to reach the semis at his home Slam would've been special.

“I do know (Roddick) is always rooting for us players to break through,” Isner said. “It has been a very long time. I guess I came pretty close this year. I don't have many more chances. We will see what happens next year. I think I'm going to be back and competing at these Grand Slams, and we'll have a lot of players on the American men's side still improving with their best tennis yet to come.”

Still, there is good news ahead for Isner. His wife, Maddy, is due with their first child, a daughter, on Sept. 22. Had he reached the semifinals Friday or the final Sunday, he would've gotten closer to the due date but insisted he wouldn't miss the birth of his daughter.

“As long as that baby's still in her belly, I'll be here,” Isner said after his last win Sunday.

The first set went to a tiebreak with Isner getting one mini-break and then closing it out a with a 132-mph ace.

But the heat began to get to him in the second set and he was broken in the fourth game. Speaking on ESPN, Patrick McEnroe said Isner appeared to be "staggering" around the court between points.

It's been so hot at the Open this week that even Roger Federer was sweating through his clothes during his four-set loss to journeyman John Millman that ended early Tuesday morning.

“I have never seen Roger sweat ever,” Isner said. “If he's sweating a lot and has to change clothes, then you know it's pretty humid out there.”

In the third-set tiebreaker, del Potro earned a mini-break when Isner smacked a forehand wide, giving the Argentine a 3-2 lead. When Isner later missed a forehand volley into the net, del Potro had another mini-break for 6-3. On his second set point, del Potro crushed a forehand winner that gave him a two-sets-to-one lead.

After the players took a 10-minute break following the third set allowed by the new Extreme Heat rule at this year's Open, del Potro immediately broke Isner in the second game of the fourth for a 2-0 lead.

“I take a shower and then I re-tape my ankles and then I lay down on the table and I don't want to come back against because the heat, it's impossible to play tennis,” del Potro said of what he did during the break. “With this crowd, it's too much energy.”

Isner had a break point on del Potro's serve in the fifth game but hit a forehand wide, and del Potro held for a 4-1 lead.

With Isner serving at 2-5, he smacked a forehand into the net on del Potro's second match point and soon the good friends embraced at the net.

Looking ahead, Isner won't play for the U.S. in the Davis Cup semifinals next week in Croatia, but left the door open that he could play in the Laver Cup in Chicago later this month. Mostly, he will foc on his growing family.

“No, I'm planning on not going to Davis Cup,” Isner said. “I definitely have a lot more important things going on. I wish I could be there, but I can't.”