The No. 3 seed used 30 aces to overcome his struggling return game in a 7-6 (8), 6-7 (3), 7-5 victory.

"To be honest, I'd rather not draw him in a tournament, particularly early on," Isner said. "If you're going to play a friend, you want it to be in a final like I did with Mardy (Fish) here last year." Second-seeded Kevin Anderson of South Africa, Yen-Hsun Lu of Taiwan and Luxembourg's Gilles Muller also won.

The 31-year-old Blake had few answers for Isner's powerful serves in what was their first singles match against each other.

Anderson credited his improving play near the net with helping him beat Michael Russell 6-1, 7-5. Muller used 15 aces to defeat local favorite Robby Ginepri 7-6 (6), 2-6, 6-2, and Lu held off qualifier Marinko Matosevic of Australia 3-6, 6-1, 6-2.

Fish, the top seed and defending champion, faces Nicolas Mahut of France on Thursday. No. 4 seed Xavier Malisse plays Ryan Harrison.

Isner hardly enjoyed a perfect service game, double faulting on tiebreakers in the first and second sets. Following the miscue in the second set, Blake earned four straight points before serving out for a 7-3 win.

In Baku, Azerbaijan, Vera Zvonareva cruised into the quarterfinals of the Baku Cup on Thursday when Kristina Kucova retired with a left leg injury.

The top-seeded Russian was leading 6-0, 3-0 when Kucova quit. Although she was playing with the lower part of her left leg heavily taped, she ran well in rallies but made little headway against a more powerful opponent.

Anastasia Pavlyuchenkova defeated fellow Russian Elena Bovina 6-4, 6-0. Kateryna Bondarenko stopped fourth-seeded Ekaterina Makarova of Russia 6-1, 6-4. The Ukrainian struggled in the first half of the year, winning two matches in her opener in Auckland before a winless streak that lasted until Wimbledon in June.

Georgia's Anna Tatishvili also advanced to the quarterfinals, edging Tatia Mikadze 7-6 (4), 6-3.

In Hamburg, Germany, second-seeded Jurgen Melzer of Austria swept into the quarterfinals of the German Open on Thursday by beating 15th-seeded Fabio Fognini of Italy 6-2, 6-3.

Melzer was runner-up in Hamburg last year.

Fourth-seeded Mikhail Youzhny of Russia beat German wild card Julian Reister 6-3, 6-3. He'll face No. 12 Marin Cilic of Croatia, who rallied to beat wild card Tobias Kamke of Germany 3-6, 6-3, 6-2.

Fifth-seeded Gilles Simon of France outlasted Jarkko Nieminen of Finland 7-6 (4), 3-6, 6-4.