Matteo Berrettini secured his place in the US Open quarter-finals for a second successive year with a five-set win over unseeded Alejandro Davidovich Fokina on Louis Armstrong Stadium.
Italian Berrettini, who reach the semi-finals in 2019, overcame the Spaniard 3-6 7-6 (7-2) 6-3 4-6 6-2 in New York.
Davidovich Fokina suffered a knee injury when trailing 4-2 in the fifth set and could not fight back.
Berrettini will face Norway's Casper Ruud who beat France's Corentin Moutet.
The fifth seed ended the lucky losers' fairytale run to a maiden Grand Slam fourth round, winning 6-1 6-2 6-7 (4-7) 6-2.
Moutet, the world number 112, was the first men's lucky loser to play in the last 16 at a Grand Slam since Stephane Robert at the 2014 Australian Open.
French Open finalist Ruud, ranked seventh in the world, is one of four players in contention to be world number one at the end of the tournament.
Later on Sunday, current world number one Daniil Medvedev, the defending champion, faces Wimbledon finalist Nick Kyrgios in the first match in the Arthur Ashe Stadium night session.
The other men's singles match is Spain's 12th seed Pablo Carreno Busta playing Russian 27th seed Karen Khachanov.
Berrettini hoping to finish 2022 how it started
The 13th seed, the 2021 Wimbledon finalist, is aiming to finish a frustrating 2022 season in style.
Berrettini reached the Australian Open semi-finals in January, reaching a career-high ranking of sixth in the world, before his progress was halted by injury.
He missed the French Open after hand surgery, returning to win in Stuttgart and at Queen's on the grass in the lead-up to Wimbledon where he was among the favourites. However, he was forced to withdraw with Covid-19.
Berrettini arrived in New York having lost his first-round matches on the hard courts of Montreal and Cincinnati but has fought his way into the second week.
Having beaten Andy Murray in the third round, Berrettini started slowly on Sunday, going a set and a break down against the world number 39.
But the 2021 Wimbledon finalist responded well, taking the second set on a tie-break and seemingly establishing control by adding the third.
Davidovich Fokina forced a decider but Berrettini wrestled back the momentum, breaking for 2-0 before a knee injury began to hinder his opponent.