First, Kyrgios will need to beat Pierre-Hugues Herbert, and Federer will need to get past Benoit Paire.
But Federer's first service game in the second - in which he battled 14 minutes and saved six break points - proved prophetic. "I'm very pleased to be back in NY, of course".
David Ferrer retired (from the game against Rafael Nadal) for the first time in a Grand Slam on his last ever Grand Slam match.
The No. 2-seeded Federer is seeking his sixth title at the U.S. Open, but first in a decade.
"It was a game with quality content and I was able to get off to a good start", Nishikori said.
"I have so much respect for Roger and everything he's done for the game". "Almost time to retire - but not yet".
The players took a 10-minute break between the third and fourth sets to help them cope with temperatures climbing above 90 degrees Fahrenheit (30 degrees Celsius).
But Federer said he's resigned to the questions, which first started cropping up nearly a decade ago.
If Federer, who made short work of Yoshihito Nishioka in the first round, gets the job done in the afternoon heat on Arthur Ashe Stadium he could book a third-round meeting with Nick Kyrgios - if the risky Australian gets past France's Pierre-Hugues Herbert. Federer raced to a 3-0 lead in the second set as well as his dominance continued to grow more and more as the game progressed.
"I'd like to play like Novak Djokovic", Tyson told SecondsOut. "I changed plans and said, 'Let's go early to America and prepare over here in the conditions that I'm actually going to see during the Open'".
"That was meaning, like, 'I never lost a first-round match here at the Open". Her second-round opponent is Czech qualifier Muchova, who beat Ukranian Dayana Yastremska in straight sets in her first-round match. "I spend the least possible time here on site because that takes energy away", Zverev said.
"It's never easy and obviously the conditions are tough for everyone because of the heat and humidity", Zverev said in an on-court interview.
In the other quarter of the bottom half of the draw, No4 seed Zverev reached the third round in NY for the first time with a 6-4, 6-4, 6-2 win over lucky loser Nicolas Mahut, 15 years his elder.
The duel between Federer and Paire will be their seventh as professionals, with a 6-0 advantage for the former world number one.
The Serb, who beat Sandgren in straight sets at Wimbledon this year, will hope for a more coherent performance out of the blistering daylight heat.
"We've had some brutal matches over the years, always super tight..."
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