Atlanta - Second-seeded John Isner beat Canada's Vasek Pospisil 6-3, 6-4 on Wednesday night in his opening match in the Atlanta Open.
Coming off a victory on Sunday in the Hall of Fame Open in Newport, Isner is seeking his fourth Atlanta title in five seasons.
He lost to Nick Kyrgios in the final last year.
Isner set up a quarter-final match at Atlantic Station against Slovakia's Lukas Lacko, a 6-3, 6-1 winner over sixth-seeded Donald Young.
The American has 11 career titles - all at the ATP World Tour 250 level.
Third-seeded Gilles Muller of Luxembourg and Tommy Paul also reached the quarter-finals.
Muller beat France's Quentin Halys 6-4, 6-7 (1), 6-3, and Paul topped Tunisia's Malek Jaziri 6-7 (5), 6-4, 6-3.
In the top half of the draw, top-seeded Jack Sock will open play on Thursday with a second-round match against Israel's Dudi Sela.
Results on Wednesday in the ATP BB&T Open at Atlanta, Georgia (x-denotes seeded player):
Tommy Paul (USA) bt Malek Jaziri (TUN) 6-7 (5/7), 6-4, 6-3
Gilles Muller (LUX x3) bt Quentin Halys (FRA) 6-4, 6-7 (1/7), 6-3
Lukas Lacko (SVK) bt Donald Young (USA x6) 6-3, 6-1
John Isner (USA x2) bt Vasek Pospisil (CAN) 6-3, 6-4