On Wednesday, the 29-year-old will be playing in his first Wimbledon quarter-final since 2013, when he went on to lose to Novak Djokovic in an epic semi-final. Nadal and Del Potro slugged it out in a quarter-final that lasted nearly five hours, with Nadal eventually winning 7-5, 6-7 (7-9), 4-6, 6-4, 6-4.
Last night, he couldn't quite edge the Spaniard, who prevailed 7-5, 6-7 (7-9), 4-6, 6-4, 6-4 in a little under five hours.
With Roger Federer knocked out by Kevin Anderson, who faces John Isner in the other semi-final, both Nadal and Djokovic have an ideal opportunity to add to their Slam collections.
Del Potro broke and served for the set at 5-4, but double-faulted and Nadal clinched the break-back with a rasping forehand down the line.
It will not quite be attack versus defence in the women's semi-final between Jelena Ostapenko and Angelique Kerber, but there will be contrasting styles on show and it is intriguing to see which will reign supreme.
Nadal kept picking himself off a slippery and dusty Centre Court surface and stood tall in the end as he triumphed over the Argentine in four hours and 48 minutes. "It's going to help my volleys when I'm at the net stay a little bit lower, these kind of things".
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Del Potro threw everything he could at Nadal in a pulsating match and even conjured the shot of the tournament as he acrobatically dived to his right to hit a fizzing forehand volley that ended a spellbinding 23-shot rally.
The big-serving Argentine pushed the double Wimbledon champion to the very limit on Centre Court and the tie had a rather anti-climatic ending.
The other semi-final will pit two-time champion Nadal against three-time victor Djokovic. He is prepared. He had a great clay-court season and although these are different courts, his resistence is in very good condition.' About Nadal vs Djokovic, the former world No.
"I sat back in the fifth and said "don't be a fool and say anything, just let these guys do their thing". He had one more chance but again the Argentinian sent down a big serve and then, when his own chance came, Del Potro drilled a bullet forehand off the top of the net and onto the sideline. In some ways he deserves to win as well. I know in the semi-finals of Wimbledon you will not have an easy opponent in front (of you).