The Spanish player needed two hours and 54 minutes to avenge his 2017 loss to Isner in the same tournament.
Also Wednesday, World No. 21 Fognini defeated World No. 8 Dominic Thiem of Austria 6-4, 1-6, 6-3 in over two hours and six minutes.
After the match, Theim said it "was a very intense fight, basically from the beginning to the end. So I'm disappointed that I lost, obviously. But game-wise, I'm not really disappointed."
(This story has not been edited by Business Standard staff and is auto-generated from a syndicated feed.)