The 13th-seeded Isner hit 30 aces and saved the only break point he faced in a 7-6 (5), 6-4, 6-2 victory over 77th-ranked Jan-Lennard Struff of Germany on Thursday at Flushing Meadows.
In a true - and, as Isner put it, ''weird'' and ''bizarre'' - example of the luck of the draw, he now will face the 22nd-seeded Kohlschreiber, who advanced when his opponent, Michael Llodra, stopped because of an injured left elbow.
It will be the third year in a row Isner plays the exact same guy, Kohlschreiber, in the exact same round at the U.S. Open. Kohlschreiber eliminated Isner in five sets in 2012, and in four sets in 2013.
As Isner pointed out Thursday, he has won the pair's four career meetings at other sites.
This annual reunion is not unprecedented.
According to the ATP, there are other examples of men playing each other over and over in the same round at the same event.
One example: Roger Federer met Novak Djokovic in the U.S. Open semifinals four consecutive times from 2008-11.