Miami - Kei Nishikori fell victim to the big game of John Isner on Thursday, the 29th-ranked American beating Japan's world number five 6-4, 6-3 to reach the Miami Masters semi-finals.
Isner became the first American man to reach the final four of the hardcourt tournament since Mardy Fish in 2011.
Nishikori, the 2014 US Open runner-up, had never faced the monster serve of Isner and was unable to cope with 12 aces off the big man's racquet -- the final one coming on match point after 70 minutes.
Nishikori managed only five winners while Isner piled on 33 and maintained his perfect record on serve in the tournament.
Nishikori reached the Miami semi-finals a year ago after beating David Ferrer and Roger Federer, but was unable to play his scheduled match against Novak Djokovic due to a groin injury.
The top Asian player suffered only his fifth loss of the season against 20 wins and a title in Memphis.