Del Potro booked his place in the semi-finals of the 2017 US Open with a 7-5, 3-6, 7-6 (10/8), 6-4 win over Roger Federer.
Many were hoping the semi-final match would be contested between Nadal and Federer for the first time ever in New York.
But the Argentine crushed these hopes with an impressive performance at the Arthur Ashe Stadium.
Del Potro won the US Open title back in 2009, beating Federer in the final.
On the way to winning the Grand Slam, he breezed past Nadal in straight sets – winning 6-2, 6-2, 6-2.
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And he is hoping to recreate a performance like this when he locks horns with the world No. 1 to battle for a place in the final.
“I played him in 2009 as well and hopefully I can repeat the result,” Del Potro said.
“We look older, Rafa is playing a great season and is No1 in the world but with this amazing support anything can happen.”
Nadal booked his place in the next round with a straight sets victory over Andrey Rublev, winning the contest in just 97 minutes.
The winner of Nadal-Del Potro will face either Kevin Anderson or Pablo Carreno.