Fifth-seed Stefanos Tsitsipas 's Cincinnati Masters challenge ended in the second round on Wednesday as he was beaten 6-4, 6-7(5), 7-6(6) by unseeded German Jan-Lennard Struff .
Struff, who has yet to win an ATP singles title in his decade-long career as a professional, was on top for most of the match against the 21-year old Greek.
He served for the match in the second set but Tsitsipas managed to stay alive by taking the second set on a tiebreak.
However, the German refused to give up and sealed the win to set up a last 16 meeting with ninth-seed Daniil Medvedev, who beat Frenchman Benoit Paire 7-6(2), 6-1.
Among the other surprises on Wednesday, world number five Kei Nishikori was beaten 7-6(2), 6-4 by Japanese qualifier Yoshihito Nishioka.
World number one Novak Djokovic and third seed Roger Federer advanced to the last 16 on Tuesday.