Until last month, Poynton had been involved in every game for Derbyshire this season. However, the ankle flared up again and is expected to require further surgery, with Poynton deciding it will no longer hold up to the rigours of playing professionally.
"It's been a really difficult decision to retire from the game I love, but the medical diagnosis and advice means I know that it's the right decision," Poynton said. "I'm grateful to everyone in the Derbyshire cricket family and further afield who have helped me during my career, both on and off the field.
"I've loved playing for Derbyshire, a club I've been associated with for over 10 years, and I'm sad to leave. I now need to focus on the next stage of my life after cricket. There's a few opportunities that I'm going to pursue and I'm excited about what lies ahead."
Poynton came through Derbyshire's academy, representing England Under-19s and going on to play more than 100 matches for the county. He made his Derbyshire debut aged 17 and in 2012 was involved in the third-highest ninth-wicket partnership in first-class history, putting on 261 with Wayne Madsen and scoring his maiden hundred.
In all, Poynton scored 1155 runs in first-class cricket, to go with 107 catches and 10 stumpings. While recovering from his injuries during the 2014 season, he worked in the club's marketing department.
Derbyshire's chief executive, Simon Storey, said: "Tom is a model professional and leaves the club with a gap to fill on and off the field. He is a natural leader and fine cricketer who has overcome great personal tragedy in the process of representing his home county.
"He has shown huge commitment and courage to get back playing first-class cricket at Derbyshire and on behalf of the whole club - members, sponsors, supporters and staff - we all wish Tom every success in the future."