Czech 15th seed Tomas Berdych was knocked out of the US Open in four sets by Ukraine's Alexandr Dolgopolov.
World number 64 Dolgopolov triumphed 3-6 6-1 7-6 (7-5) 6-2 in New York.
Berdych hit 57 unforced errors, 12 double faults and had a first-serve percentage of only 45% on court 17 at Flushing Meadows.
Dolgopolov, 28, will face Victor Troicki in the third round after the Serb beat Italy's Stefano Travaglia 7-6 (8-6) 7-5 6-0.
The Ukrainian said on Wednesday he gave his "best effort" in a match at the Winston-Salem Open last week that is being assessed for suspicious betting patterns.