The 14th seed dodged heavy rain and swirling winds by playing under a closed roof at the Qizhong Tennis Center, but struggled to impose his heavy-serving game on the 83rd-ranked Colombian in a performance strewn with errors.
The 2.08m tall Isner — the top player in the US — lost the first set 6-4, but dug deep to win the second 7-5, leveling the match on his seventh set point.
Isner, who fired down 29 aces, but made 32 unforced errors, broke Giraldo in the 12th game of the decider to take it 7-5.
Earlier, Spain’s Marcel Granollers was a 6-4, 6-4 winner over out-of-sorts Serbian Janko Tipsarevic, who required attention from the physio for an apparent left-ankle problem.
Granollers, 36th in the world, broke the bespectacled Tipsarevic, ranked 12 places higher, early in both sets, which proved decisive.
In the late match yesterday, France’s Gael Monfils cruised past Japanese qualifier Tatsuma Ito 6-3, 6-2.
Roger Federer, seeded fifth in the singles, teamed up in the doubles competition with China’s Zhang Ze, ranked 271st in the world, and they cruised to a 6-2, 6-1 victory over South Africa’s Kevin Anderson and Dmitry Tursunov of Russia.
The Swiss 17-time Grand Slam winner, who has slipped to seventh in the singles rankings, is in danger of missing out on next month’s end-of-season ATP World Tour Finals in London for the first time since 2001.
He faces a potential quarter-final meeting with defending champion and top seed Novak Djokovic, who has dropped one place to world No. 2 behind Rafael Nadal, despite beating the Spaniard in the final of the China Open on Sunday.
The top eight seeds in Shanghai all have a bye through to the second round.
Typhoon Fitow slammed into China’s east coast yesterday, packing winds of more than 200kph and bringing drenching rain, forcing changes to the scheduling of the tournament.