It took the world No. 5 two hours and nine minutes to win the match on the Philippe Chatrier court.
At the end of the match, the Spaniard, who has won a record 21 Grand Slam titles, was reassuring about the condition of his left foot, which had betrayed him ten days earlier in Rome.
"I think I've already talked enough about my health before the tournament. I'm in the competition. I answer the questions every time because I respect you. Now I prefer to talk about tennis and we'll see what happens on the physical side, how I can handle things," he told the media.
"I'm really thinking about tennis now because if I worry about my health every day, I won't be able to go very far in the tournament," said the Spaniard, who played his 300th Grand Slam match of his career Wednesday night.
In the third round, Rafael Nadal will face Dutchman Van De Zandschulp, ranked 29th in the world, who defeated Fognini (6-4, 7-6, 3-2) after the Italian retired.