The Spaniard was extended into a third set by Isner, but quickly regained command to seal a 7-6 4-6 6-3 win in the third round.
Making his return to the clay courts, Nadal had eased past??Lucas Pouille in his opening clash, and received a more testing workout against the American powerhouse.
In a tense opener, Nadal was forced to save two set points before he edged out Isner in the tie-break.??
But the Florida man mounted a determined response in the second set, breaking the eight-time winner to level the match.
Any doubts about Nadal’s fragile fitness were answered in the third as he broke Isner’s booming serve again and powered to victory with his trademark ground strokes.
He will next face David Ferrer or Gilles Simon in the last four.