Every single set was hard-earned, with Nadal taking the first 7-5 before Del Potro evened things up on a tiebreak in the second.
The last-16 tie between Del Potro and Frenchman Simon was suspended overnight due to darkness on Monday with the Argentine fifth seed two sets to one ahead.
Del Potro was thrashed by the Spaniard in the French Open semi-final last month but feels his game matches up better against the world number one on grass despite losing their only two meetings on the surface. And so it proved in a match that got better the longer it went as he ground out a 7-5, 6-7 (7), 4-6, 6-4, 6-4 win in four hours and 47 minutes, the longest of the tournament. In the next game, Nadal staved off two break points, the first when he used his never-give-up-on-a-ball defence to stretch a point and del Potro pushed a forehand way long.
Now Nadal will face longtime rival Novak Djokovic in the semifinals Friday.
But Nadal was first to break in the deciding set and he built a 5-3 advantage with a looped forehand victor before confirming his final four place with a volley after four hours and 48 minutes.
Nadal soon returned the favour with a break of his own, before another hold left Del Potro rattled.
"Rafa is a fighter", del Potro said.
Soon, Nadal gained the upper hand, shaking off a hard fall onto his back on one point by whipping a cross-court backhand victor on the next to break for a 3-2 lead.
Simon saved a fourth match point when he threw the kitchen sink at a forehand return and he eventually took his fourth break point to level at 5-5.
"It was a very emotional match. great quality tennis, especially in the last set there were some incredible points". Raonic hit 31 aces to Isner's 25 but was broken three times, including the last game of the match.
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