World number 36 Reilly Opelka came back from dropping the first set to defeat defending champion and top seed Daniil Medvedev 2-6, 7-5, 6-4 at the St Petersburg Open on Thursday.
The giant American also saved four break points in the deciding set before going on to complete the biggest win of his career against the world number six.
“It’s always a tough match, playing one of the best players in the world in general, but especially at his home. It’s a great win for me,” said Opelka.
“It was ugly for the first set-and-a-half. I felt like I barely won any points on his serve, but part of that is just because of my opponent... Daniil is an absolute nightmare to play, especially for a guy like me because he just runs every ball down.”
It was Medvedev’s third defeat in four matches having made opening round exits in Hamburg and Roland Garros.
Opelka will next face last year’s runner-up Borna Coric after the seventh-seeded Croat enjoyed a 6-3, 7-5 win over Russian wild card Roman Safiullin.
Reilly Opelka (USA) bt Daniil Medvedev (RUS x1) 2-6, 7-5, 6-4
Borna Coric (CRO x7) bt Roman Safiullin (RUS) 6-3, 7-5
Karen Khachanov (RUS x4) bt Aslan Karatsev (RUS) 4-6, 7-5, 6-3
Milos Raonic (CAN x6) bt Alexander Bublik (KAZ) 6-3, 6-2
Andrey Rublev (RUS x3) bt Ugo Humbert (FRA) 4-6, 6-4, 7-5
Denis Shapovalov (CAN x2) bt Ilya Ivashka (BLR) 6-1, 6-4