Fifth seed and Wimbledon runner-up Milos Raonic of Canada was knocked out of the US Open on Thursday by American qualifier Ryan Harrison.The 120th-ranked Harrison won 6-7 (4/7), 7-5, 7-5, 6-1 and goes on to face Cypriot Marcos Baghdatis for a place in the last 16.
"It was extremely physical out there but I was playing on adrenaline," said 24-year-old Harrison who was as high as 43 in the world in 2012."This is a big win for me. I have been playing well all summer."
Raonic, considered as a potential title dangerman in New York, hit 18 aces and 69 winners but committed 62 unforced errors.
Harrison has now reached the third round of a grand slam event for the first time after recording just a second win over a top 10 opponent in 27 meetings.
Novak Djokovic made the last 32 of a major for the 33rd successive time without hitting a ball at Flushing Meadows.
Djokovic was handed a walkover when Jiri Vesely of the Czech Republic withdrew from their second round encounter suffering an inflammation of the left forearm.
Vesely's misfortune was a welcome boost for world number one Djokovic who had required treatment on his upper right arm in his laboured first round win over Jerzy Janowicz on Tuesday (AEST).
Left-hander Vesely had defeated the Serb at the Monte Carlo Masters in April.
Djokovic will now face 34-year-old Russian Mikhail Youzhny - twice a semi-finalist - for a place in the last 16.
"I'm very, very disappointed right now," said 23-year-old Vesely. "I was looking forward to playing Novak, I would have nothing to lose."Djokovic's walkover resulted in France's Gael Monfils' match with Czech Jan Satral being moved to Arthur Ashe Stadium, and Monfils continued his strong start to the Open with a straight sets win, 7-5, 6-4, 6-3 in just under two hours.
There was more good news for home fans with 20th seed John Isner defeating Belgium's Steve Darcis - who beat Australia's Jordan Thompson in round one - 6-3, 6-4, 6-7 (12-10), 6-3.
South African 23rd seed Kevin Anderson beat Canada's Vasek Pospisil in straight sets, 7-6 (7/3), 6-4, 6-4, but a trio of seeded players departed.
Baghdatis earned his spot against Harrison with a 6-2, 6-4, 3-6, 6-4 win over 32nd seed Benoit Paire of France.
Russia's Andrey Kuznetsov accounted for Spanish 31st seed Albert Ramos 7-5, 6-4, 7-6 (7/5), while Ramos' compatriot Nicolas Almagro beat Uruguay's Pablo Cuevas (18) 7-6 (7/5), 6-4, 7-6 (11/9).