Del Potro been suffering with wrist problems ever since winning the US Open eight years ago.
But he looks close to his best in this year’s tournament, having not lost a set before his fourth round match against Dominic Thiem.
The Argentine came back from 2-1 down and saved two match points to beat the world No 8 in a scintillating five-set match.
Federer had a relatively simpler route into the last eight, beating Philipp Kohlschreiber in straight sets.
This will be the 22nd time Federer and Del Potro will meet on the ATP World Tour and the last time they met at the US Open was in the 2009 final with the latter coming out triumphant.
It was a match that went down in Grand Slam history with it going to five sets.
And Federer is looking forward to hopefully recreating a similar atmosphere once he takes to the court again against Del Potro.
“I figured that they were in the fifth set, so that’s when I knew Del Potro had won,” Federer said.
“It’s great to see him back on the tour.
“He has had a rough ride for a lot of years with his wrists, so to see him back on tour, happy, winning and beating the best players in the world like Thiem is wonderful for our sport.
“He’s a good guy and I played him this year in Miami and we had a good match, so to play him here again after our epic finals in 2009 is great for both of us.
“We’ll both be looking forward to it. Well, at least I am.”