MASON, Ohio (AP) -- Novak Djokovic dumped another pressure-packed shot into the net and stood in place for a moment, stunned by another upset in Cincinnati.
It's the only place where he can't win.
Top-ranked American John Isner ended Djokovic's attempt to make ATP history Friday, beating the No. 1 player 7-6 (5), 3-6, 7-5 in the quarterfinals at the Western & Southern Open.
Djokovic has never won in Cincinnati, the only Masters event that has eluded him during his career. He has lost in the finals four times, including last year to Roger Federer. All he needs to do is hoist the winner's trophy one time in Cincinnati to become the first player to win all nine Masters events.
Wait until next year. Again.
"It's disappointing that I played this way,'' Djokovic said. "For me, it's very disappointing.''
Isner reached the semifinals in Cincinnati for the first time, knocking off a No. 1 for only the second time. His other No. 1 upset? He beat Djokovic at Indians Wells in the semifinals last year.
"A fantastic win for me,'' Isner said. "Certainly one of my greatest memories as a tennis player.''
He'll play seventh-seeded Juan Martin del Potro, who advanced Friday by beating qualifier Dmitry Tursunov 6-4, 3-6, 6-1. Del Potro is in the semifinals for the second straight year.
Soon after Djokovic got knocked out, No. 2 Andy Murray was gone, too. He failed to convert a break point while losing to Tomas Berdych 6-3, 6-4. Berdych also beat Murray in the quarterfinals at Madrid this year.
In the women's draw, 14th-seeded Jelena Jankovic beat 12th-seeded Roberta Vinci 6-0, 6-4 to reach the semifinals for the third time. She won the tournament in 2009 and lost the title match to Maria Sharapova in 2011.
"I love playing here in Cincinnati because I have great results in the past,'' said Jankovic, who fought off eight of nine break points in the second set. "So that always helps. I mean, I was a finalist and a champion before, so you always love coming back to places where you can win.''
He played poorly last year in his loss to Federer in the final. He was off again Friday, which was especially frustrating since he came into the tournament motivated to make ATP history.
"I just played a very bad match overall,'' he said. "Terrible match. From beginning to end, except the start of the second set, I was just a different player totally.''
Djokovic wasted a chance to break Isner early in the third set. He was up 40-15 in the final game, ready to send it to a tiebreaker, when he came apart. Isner kept the game going with a running forehand that hugged the line, drawing a loud cheer from the crowd.
"Probably the best shot I hit all match,'' Isner said.
Djokovic gave Isner his first attempt at a match point by dumping a backhand into the net, but saved it with a 119 mph ace. With the crowd cheering Isner on, Djokovic double-faulted and dumped another backhand into the net, giving Isner his only service break of the match.
What happened on those last two points?
"I don't know,'' Djokovic said.
Del Potro has been playing with a sore wrist and knee, two concerns with the U.S. Open at hand. He managed to reach the semifinals without issue.
"It's bothering me a little bit, but not too much,'' he said. "(I'm) trying to play a slice and play different shots in this tournament before the U.S. Open to see how different I can play against the top guys or doing different things.''
"I'm OK,'' he added. "My knee is OK, too, and that's important looking forward to New York.''
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