Nadal is the heavy favourite to progress as he hunts for his fourth crown at Flushing Meadows.
The Spaniard progressed to the second round after David Ferrer retired during the second set of their clash on Tuesday night.
He now faces Pospisil with the pair only meeting once before, Nadal winning that clash in Beijing three years ago.
But the Canadian is hopeful of causing an upset on Arthur Ashe Stadium.
“I have not had the best couple of years but now I am playing my best tennis,” Pospisil told TSN.
“I am playing great on the court. It was difficult with the humidity but I am happy where my game is at.
“I feel like I’m improving. I’m a better player now than a few years ago, even if the ranking doesn’t show it.
“I feel lighter and am working hard. I know the best years are ahead.”
Pospisil, ranked No 88 in the world, beat Lucas Lacko in straight sets to reach the second round of the US Open for the third time in his career.
Rafael Nadal vs Vasek Pospisil LIVE updates
02.05: Serena Williams has just waltzed her way through to the third round and it’s not long now until Nadal and Pospisil make their way on to court at the Arthur Ashe Stadium in New York.
02.00: Welcome to Express Sport’s live coverage as Rafael Nadal and Vasek Pospisil face off in the second round of the US Open.