Isner, no stranger to marathon contests having been involved in the longest professional tennis match of all time at Wimbledon two years ago, saved five set points in taking the second set of the all-American clash.
The 26-year-old advances to face another American, Ryan Sweeting. Another local favourite, Andy Roddick, came from behind to claim a three-set win over Germany’s Philipp Petzschner. Fourth seed Roddick failed to make the most of his chances as he lost the first set, but stormed back to claim a 4-6, 6-4, 6-1 victory.
Second seed Marin Cilic and third seed Viktor Troicki were both dumped out of the tournament. Cilic, making his 2012 debut following injury, lost 6-3, 3-6, 6-2 to Jarkko Nieminen of Finland, while Troicki bowed out 6-4, 4-6, 6-4 at the hands of Belgium’s Steve Darcis.
Three other seeds, Philipp Kohlschreiber, Alex Bogomolov jnr and Kevin Anderson, advanced.