Former world number three Milos Raonic pulled out of the Japan Open with a calf strain on Thursday, just two days after returning from a seven-week layoff that followed surgery on his left wrist.
Seeded third, the Canadian was forced to retire after one game of his second-round match against local hope Yuichi Sugita.
"I picked up a strain to the calf. It's hard to know the extent of it," Raonic told the ATP World Tour website.
ATP New York
Edmund wins through to New York Open quarter-finals
"It happened when the score was deuce, I felt a sharp pain at the back of my leg. I will head home now and get medical attention."
A three-time former finalist in Tokyo, Raonic beat Serbia's Viktor Troicki 6-3 6-4 in Tuesday's first round.
The Canadian won the last of his eight career titles in Brisbane last year and has since dropped out of the top 10.
"It's been a difficult and frustrating year, I obviously wish I could have focused on tennis more rather than chasing help all the time," Raonic said.
"My wrist isn't a concern... It was kind of a growth that happened over time. Therefore, it was very simple and something that needed the swelling to go down."
Earlier, Shenzhen Open champion David Goffin scored a 2-6 7-5 7-6(1) win over Australia's Matthew Ebden while Richard Gasquet beat Lu Yen-hsun 6-0 7-6(5).
Also advancing to the quarter-finals was American Steve Johnson, who defeated Alexandr Dolgopolov 6-2 6-4.
Djokovic pays tearful tribute to 'inspirational' Kobe after beating Raonic
Dominant Djokovic ends Raonic run to set up Federer showdown