It is the Labor Day holiday weekend in the United States but Keys and Vandeweghe along with Shelby Rogers will be hard at work trying to join Venus Williams, who advanced on Friday, into the fourth round.
No one has worked harder just to get to the third round than five-time U.S. Open champion Roger Federer, who has needed five sets in each of his first two matches and will be desperate to avoid repeating when he faces 31st seed Feliciano Lopez.
"I might feel more tired than I normally would going into a third round but that's okay," said Federer. "My preparation hasn't been good at all here. I knew I was going to maybe struggle early on.
"I still believe I'm going to pick up my game and become just more consistent because I'm not playing all that bad."
Although he has not been pushed to five sets yet Nadal has also been slow to hit his stride on the Flushing Meadows hardcourts surviving a tough three-setter against Serb Dusan Lajovic and four set test from Japan's Taro Daniel.
The Spaniard will next face lucky loser Argentine Leonardo Mayer, who is playing his first event since winning the German Tennis Championships in late July and is 0-3 against Nadal.
Pliskova will also take a perfect record against her opponent Zhang Shuai having beaten the 27th ranked Chinese in four head-to-head meetings.
Keys, seeded 15th, will be seeking a spot in the fourth round for the third consecutive year when she clashes with 17th seeded Russian Elena Vesnina while 20th seed Vandeweghe faces Poland's Agnieszka Radwanska, the 10th seed.
(Editing by Greg Stutchbury)
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