Borna Coric spoiled the return of Rafael Nadal after a five-year absence from the ATP and WTA Cincinnati Masters on Wednesday with a 7-6 (11/9), 4-6, 6-3 upset victory in the second round.
The 36-year-old Spaniard, who won the Cincinnati title in 2013, was playing his first match in well over a month after withdrawing with an abdominal injury from his Wimbledon semifinal against Nick Kyrgios.
"When you come back from injury, if you win the first match things get better," Nadal said. "That was not the case today."
Nadal began the season with three titles and 20 consecutive wins but will head into the US Open after only one summer hardcourt match.
"This tournament was difficult for me. He played better," Nadal said. "It's difficult to take a lot of positive things from this match.
"I need to practice. I need to return better. That's the truth."
The night appearance by the 22-time Grand Slam champion was interrupted for an hour and a quarter by rain in the opening set.
Once back, the pair struggled into a first-set tie-breaker which lasted for well over a quarter of an hour.
Nadal missed on two set points of his own and had to save two set points for Coric.
But on the Croat's third opportunity, Nadal handed over the set after an hour and a quarter on court with a costly double-fault.
"I had chances in the tiebreaker and I played terrible on two easy set points," Nadal said.
Nadal then took another 75 minutes to square the match thanks to a break in the seventh game of the second set.
The Spaniard was broken to trail 2-4 on a forehand wide, opening the door for Coric, who finished off the victory in just under three hours.
"It was very very special," said Coric, who had shoulder surgery last year. "I've been out the last two years injured. I didn't play on the big stage.
"I was looking forward to playing this match. It was all kind of crazy I would say."
Kyrgios, meanwhile, lost his way amid objections to on-court advertising lights, with the Wimbledon runner-up falling 6-3, 6-2 to American Taylor Fritz.
The Australian was in complaint mode from the start, lamenting the distraction of flickering LED lights on an advertising board and demanding a fix.
World number 28 Kyrgios, after a standout summer which included the Washington title this month, could not find his best game in crashing out to 11th seed Fritz after only 50 minutes.
RADUCANU ROLLS ON
Women's 10th seed Emma Raducanu dispatched her second Grand Slam champion in less than 24 hours, crushing Victoria Azarenka 6-0, 6-2.
The teenaged US Open champion claimed the first 10 games before Azarenka, a two-time Australian Open champion, finally captured a game.
But the young Briton, who ousted Serena Williams the night before with another love set, denied Azarenka on two break points in the final game to win in 63 minutes.
"It was another really difficult match and a tough matchup to play Vika," Raducanu said. "I knew I had to be really on my game. I didn't have much time to turn around.
"I'm obviously pleased with how I played today and how I stayed really focused."
Andy Murray needed a post-match on-court visit from the trainer after losing 3-6, 6-3, 6-4 to Cameron Norrie in the second round.
Three-time Grand Slam champion Murray, twice a Cincinnati champion, needed massage on his right thigh before leaving the court after battling for nearly two and three-quarter hours.
"My consistency maybe was not where I'd want it," Murray said. "But there was some positive tennis in there at times. I definitely had enough opportunities to win."
After cramping at other events in recent weeks, the 35-year-old Scotsman is worried about his physical situation.
"It's a big concern for me. It's something I need to address and find a solution for," Murray said. "You need to try and understand what's going on there."
American Ben Shelton stunned fifth seed Casper Ruud, defeating the Norwegian 6-3, 6-3, while women's world No 1 Iga Swiatek beat Sloane Stephens 6-4, 7-5.