The second-seeded American managed only five of those aces in dropping the first set. Isner, making his debut at this event at The Racquet Club, bounced back by serving up 11 aces in the second set, during which he won all 15 points on his first serve. He had 10 more aces in the third set, winning 17 of 18 points on first service.
Ryan Harrison upset fellow American and No. 3 seed Sam Querrey 6-3, 6-1 in 54 minutes. Harrison won the first five games and broke Querrey twice in taking the first set 6-3. Then he broke Querrey twice to go up 4-0 in the second set, before finishing out the match.
Donald Young beat fellow American Reilly Opelka 7-6 (3), 6-3 earlier Wednesday. Nikoloz Basilashvili of Georgia beat Australia's Jordan Thompson 6-3, 6-0 and will play top-seeded Ivo Karlovic on Thursday. Mikhail Kukushkin of Kazakhstan downed Germany's Benjamin Becker 6-3, 6-4.