The big Argentine was feeble in the opening set, winning just one game, but he picked up the pace to claim a 1-6 6-1 6-2 6-4 victory on Court Suzanne Lenglen.
Del Potro, whose career has been plagued by wrist injuries, withdrew from the this month's Rome Masters with a groin injury, sparking fears about his prospects in Paris.
When he lost the first set in 25 minutes it looked ominous for the 29-year-old but there looked nothing wrong with his movement as he powered past the world number 116.
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Former U.S. Open champion Del Potro is playing at Roland Garros for only the second time since 2012 and will be a danger in the top half of the draw.
(Reporting by Martyn Herman; Editing by Ken Ferris)
