Hopes of a home winner in the men's singles at the US Open were ended as John Isner was beaten by Fernando Verdasco.

The big-serving American started well enough but, perhaps understandably given his four-hour victory over Andy Roddick on Saturday night, he faded as the match wore on and went down 4-6 6-4 6-4 6-4.

Verdasco, who made the semi-finals at this year's Australian Open, progresses to the last eight at Flushing Meadows for the first time. He will next face either Novak Djokovic or Radek Stepanek.

The players traded early breaks before Isner took his next chance to deservedly win the first set.

But Verdasco was not perturbed by the partisan crowd on the Louis Armstrong Stadium and he hit back by taking the second.

The Spaniard then moved ahead in the third and although Isner saved a set point on his own serve at 3-5, Verdasco remained focused and served out to love to gain the upper hand in the match.

He refused to let his grip slip and broke in the fifth game of the fourth set before serving out the rest of the match, clinching it when Isner sent a forehand long after two hours and 26 minutes on court.