That's why Isner was relieved to put this match behind him.
The No. 3 seed used 30 aces to overcome his struggling return game in a 7-6 (8), 6-7 (3), 7-5 victory over Blake in the second round of the Atlanta Tennis Championships on Wednesday night.
"It's always fun playing doubles with him and I think we had a lot of fun last night," Isner said. "To be honest, I'd rather not draw him in a tournament, particularly early on. 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."
The 31-year-old Blake had few answers for the 6-foot-9 Isner's powerful serves in what was their first singles match against each other.
"That's his game," Blake said. "He's got a huge serve, and his returns aren't the best part of his game, but he served well when he needed to and made a couple of big returns and played some great points at 5-all in the third set."
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 of nearby Kennesaw 7-6 (6), 2-6, 6-2, and Lu held off qualifier Marinko Matosevic of Australia 3-6, 6-1, 6-2.
The 26-year-old Isner hardly enjoyed a perfect service game, double-faulting on tiebreakers in the first and second sets. Following Isner's miscue in the second set, Blake earned four straight points before serving out for a 7-3 win.
Isner was coming off his second ATP title, winning July 10 on grass at the Hall of Fame Championships in Newport, R.I., where he didn't lose a set.
"Confidence was the difference tonight," Isner said. "During the big points of the match, I played my best. From 5-all with him serving 40-15 where he double-faulted, those three points I played from 40-30 him, deuce and my add were the best three points I played probably the whole match."
Anderson, ranked 34th in the world, won his first career ATP tour title earlier this year in his native Johannesburg. He improved to 26-16 on the year with his first victory in two career meetings with Russell.
"I feel I'm at a point where I have a lot more belief and confidence in my game, regardless of who's on the other side of the net," Anderson said. "I'm still working on a lot of those things. For instance, just moving forward, coming to the net a little bit more, trying to dictate play and I think if I can continue on improving on that, it's going to allow me to play my best tennis."
Muller, who will face Anderson in the third round on Friday, wasn't affected by the partisan crowd supporting Ginepri.
"It's always nice to play in front of a crowd, no matter if they cheer for him or for me or they want to see nice tennis," Muller said. "It's nice to play in front of a crowd than playing on court No. 15 and there's nobody."
Isner was just glad to get through a tough match against a close friend.
"I was hitting too many forehands inside-in to his running forehand, which was stupid because he's going to clock a winner most of the time," Isner said. "My best shot, beside my serve, is my inside-out forehand, so I felt pretty comfortable when I was in the rally hitting backhands to his forehand. Both of us are kind of similar in that regard, but that break point at the end of the match was indicative of that."