The Serbian star reaches fourth round amid growing fears about durability of his injured left hamstring.
"I can't believe it. He is definitely one of the greatest of all time," said Frances Tiafoe after beating 22-time Grand Slam champion Rafael Nadal.
Nadal had not played a competitive match since pulling out of his Wimbledon semi-final against Kyrgios due to injury in early July.
The former world number one, who will be 41 in August, has not played since July last year, when he was knocked out of Wimbledon in the quarter-finals against Hubert Hurkacz.
Rafa Nadal had said last week that daily training was a challenge and he would take a doctor with him to Paris after a chronic foot injury flared up during his defeat by Denis Shapovalov at the Italian Open.
In a clash of generations, 19-year-old Carlos Alcaraz defeated his idol 6-2, 1-6, 6-3 in the Madrid Open quarterfinals.
The Spaniard is currently recovering from a stress fracture of a rib he suffered in the Indian Wells semi-final against compatriot Carlos Alcaraz.
Rafa Nadal, 20-time Grand Slam champion, says two-week gap between French Open and Wimbledon not enough time for him to recuperate after demanding clay-court season.
Novak Djokovic handed 13-time champion Rafael Nadal only his third defeat in 16 years and 108 matches at the French Open to reach his sixth Roland Garros final after an epic showdown which even beat the country's Covid-19 curfew.
Serbian tennis player Novak Djokovic breaks Roger Federer's record for most weeks as the men's top number one, and plans to win many more Grand Slams.
US Open runner-up Medvedev, chasing his fourth ATP Tour title in a breakthrough 2019 season, will meet Germany's Alexander Zverev in Sunday's final.
World number two Rafael Nadal advanced to the US Open third round by walkover after Australian Thanasi Kokkinakis withdrew from the tournament with a right shoulder injury.
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