The top-seeded Roddick is a three-time winner of the event. He will face last year's champion, No. 2 seed Juan Martin del Potro, who defeated Fernando Gonzalez 7-6 (2), 6-3 in the other semifinal.
Roddick and Isner were even through most of the third set until Roddick broke Isner to go up 6-5.
"John made me play my best tennis tonight," Roddick said. "I think anything less than that wasn't going to get it done."
Isner had skirted trouble earlier in the third set. He faced break point in the opening game and at 4-all before he fought back with his serve, closing out each of those games with aces.
"I was getting break points, I wasn't converting," Roddick said in a television interview after the match. "But it wasn't because I wasn't putting returns on the court or putting pressure on him, he was coming up with the goods."
Isner was not as lucky his final service game, hitting an attempted crosscourt forehand into the net on the second break point. It was the fifth break point for Isner in the set. Roddick then closed out the match, finishing with a backhand winner down the line.
"Every service game I held was just a battle," Isner said. "Eventually he kind of broke me down, got me at 5-all, and that was it."
Roddick only faced two break points in the match, saving both in the third game of the first set.
Both players relied on big serves. Isner had 20 aces and did not double fault, while Roddick had nine aces against one double fault.
Roddick, who entered with a 29-6 record in tiebreakers this year, had a rare tiebreaker loss in the first set. He wasted no time reasserting himself, getting the first service break of the match in the second set's opening game. He broke Isner a second time for a 5-2 lead, and evened the match with a winner that Isner let go by, thinking it was long before he watched it hit just inside the baseline.
"I started feeling a little bit tired in the second set," Isner said. "I caught my second wind in the third and it was kind of a battle."
The night match kept Roddick and Isner out of the heat that affected both del Potro and Gonzalez in the afternoon. Temperatures in the Washington area were in the mid-80s with moderate humidity for the afternoon match.
"It was very tough for both of us," del Potro said. "The court was so hot, and after the first set Fernando was so tired. I feel tired, too, but with my serve I had short points."
Gonzalez's fatigue showed early in the second set when he fell to the court during a point. Gonzalez stayed there for a moment, and when del Potro walked toward the net, Gonzalez smiled and reached out a hand. Del Potro stepped over the net and helped Gonzalez up to the cheers of the crowd.
"I was thinking, 'Lay down with him,"' del Potro said. "But if I do that, we'd never stand up."
Serving down 5-6 in the first set, del Potro faced three break points before forcing the tiebreaker. The Argentine then broke the fourth-seeded Gonzalez twice to go up 5-0 in the second set.
"It was tough, physically and mentally, after that first set," Gonzalez said. "If you win the set and you're tired, you're still high. ... When you lose that kind of set, the beginning of the next set is really important and he took the big advantage."
Del Potro picked up the first break of the match when Gonzalez double-faulted - one of his six in the match - giving del Potro a 3-2 lead in the first set. After his second serve went into the net, Gonzalez threw his racket to the ground and it bounced high in the air before settling on the court. He smashed the racket to the ground again on the side of the court between games.
Gonzalez had 34 unforced errors, and del Potro had 29 as both players struggled at times in the conditions.
"We didn't play good tennis," Gonzalez said. "We were really tired and we were missing many balls."
It will be the second meeting for Roddick and del Potro. In the final at Los Angeles last August, del Potro won in straight sets.
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