Last year's US Open runner-up Kei Nishikori crashed out in the first round in New York as France's Benoit Paire beat the fourth seed in a five-set thriller.
Paire, ranked 41st in the world, saved two match points in the fourth set before claiming a decisive break in fifth to clinch a shock 6-4 3-6 4-6 7-6 (8/6) 6-4 victory.
"It was impossible for me to imagine this, beating Nishikori," Paire said.
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"I will celebrate this with my coach, my team and my family. I am very happy."
Nishikori lost to Marin Cilic in last year's final at Flushing Meadows and his swift exit stands to benefit top seed Novak Djokovic, whom he beat in the semi-finals 12 months ago and was due to meet again in the last four.
"It's always very sad to lose but he was playing good tennis," Nishikori said.
"I don't think I played badly. I didn't play great but it's never easy in the first match. He's a good player."
Paire will now play Turkey's world number 84 Marsel Ilhan as the Frenchman bids to reach the US Open third round for the first time.