The world number one eased to a 6-4, 7-6 win against the towering American to set up a last-eight match with Australian talent Bernard Tomic, who beat Guillermo Garcia-Lopez.
The Serbain’s first thought after his straight sets win was to check his tennis gear for holes after Isner smashed an impressive eight aces past the world number one in 11 service games.
The 27-year-old, who beat Andy Murray to win the year’s first Grand Slam in Melbourne, required just over an hour-and-half to see off the challenge of home favourite Isner at Indian Wells.
Meanwhile, 17-time Major winner Roger Federer, who is seeded second at Indian Wells, eased to a 6-3, 6-2 win against Jack Sock, whilst Andy Murray and Rafael Nadal also sealed straight set wins.
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