NEW YORK — Again, John Isner’s trip to Flushing Meadows ended in the third round. Again, it happened with a loss to Philipp Kohlschreiber of Germany at that stage.

And again, there are zero American men in the U.S. Open’s Round of 16, something that never happened until last year at the country’s tennis championship, which was first played in 1881.

On a windy, cloudy evening, the 13th-seeded Isner hit 42 aces, saved all five break points he faced and yet it wasn’t enough. Unable to capitalize on plenty of openings and surprisingly outplayed in three tiebreakers, Isner lost to the 22nd-seeded Kohlschreiber, 7-6 (4), 4-6, 7-6 (2), 7-6 (4).

“It’s disappointing for me personally, not for America as a whole,” Isner said.

It was the third straight year these two men faced each other in the third round in New York, and Kohlschreiber won them all. He eliminated the big-serving, 6-foot-10 Isner in five sets in 2012, and in four sets in 2013

Isner only converted 1 of 12 break points.

“Got a little tight, to be honest, and didn’t move my feet on some points that I really needed,” Isner said. “I had chances. I just didn’t convert.”

Isner, 29, is best known for winning the longest match in tennis history, an 11-plus-hour marathon spread over three days that ended 70-68 in the fifth set at Wimbledon in 2010.

Currently he is the only U.S. man ranked in the top 45.

This one mainly came down to the tiebreakers, usually a strong suit for Isner: He entered the day 37-17 in those set-deciders this season while Kohlschreiber was only 9-11.

“He was just better,” Isner said. “I’ve got to be better. I know I can be. Just not showing it.”

Earlier Saturday, 57th-ranked Sam Querrey – entering the day, the only other man from the host country remaining of the 12 in the draw – put up little resistance while bowing out against No. 1 Novak Djokovic, 6-3, 6-2, 6-2.

Kohlschreiber will face Djokovic in the fourth round.

Given Isner’s history against Kohlschreiber at the U.S. Open, it’s tough to call that result surprising, even if the American is ranked higher and is 4-0 against the German everywhere else.

Instead, look to the women for the “Did that really happen?” results. In the latest of a series of stunners, third-seeded Petra Kvitova, who won her second Wimbledon title last month, was sent home with a 6-4, 6-4 defeat against Aleksandra Krunic, a 21-year-old qualifier from Serbia who is ranked 145th.

That means that the women seeded 2, 3 and 4 behind No. 1 Serena Williams are all gone before the end of Week 1.

Of the top eight women, only Williams, No. 5 Maria Sharapova and No. 7 Eugenie Bouchard remain. Bouchard reached the fourth round at the U.S. Open for the first time by beating 30th-seeded Barbora Zahlavova Strycova, 6-2, 6-7 (2), 6-4.

Williams is the last American singles player left; there were 17 in the women’s draw, and she’s beaten three, including a 6-3, 6-3 victory against Varvara Lepchenko on Saturday.

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