The 31-year-old tore his achilles in the Magners League match against Leinster in March and the injury has not healed well enough for him to resume playing at the highest level.
Powell becomes the second Blues player forced into retirement this season, after Gareth Cooper’s announcement earlier this year.
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He played for Wales Schools before joining Cardiff RFC in 1999 and went onto play 44 first-team games before moving to Richmond.
During his career, the tight head prop also played for Leeds Tykes and Gloucester before returning to Cardiff Blues in 2006 and playing a further 80 matches for the top side in the Welsh capital.
Powell now joins former Wales and British & Irish Lions scrum half Gareth Cooper in hanging up his boots this season. Cooper left the club after failing to overcome a nagging groin problem that had forced him to undergo three separate operations earlier in his career.
“I’ve worked extremely hard to overcome this injury but, in the end, I’ve been advised by my consultant that my achilles will not stand up to the demands of the game. It is hugely disappointing,” said Powell
“I have played with some great players and made many lifelong friends throughout my career. There have been huge changes at Cardiff Blues since I first joined in 1999 and I wish them every success in the future.”
“Playing rugby has been a large part of my life for many years since I first started at Treherbert RFC. However, I have a young family and it is now time to look to the future and enjoy the next chapter of my life.”