Andrew Flintoff has announced his retirement from all forms of cricket "with disappointment and sadness".
The injury-plagued all-rounder, 32, revealed the decision came after consultation with medical advisers.
He said: "Having been told my body would no longer stand up to the rigours of cricket, I had no alternative."
Lancashire star Flintoff played a key role in England's Ashes successes of 2005 and 2009 but had been dogged by knee problems in recent years.
He added in a statement: "I was told the problems I have been trying to overcome in rehab for the last year, following the latest of a series of operations, would not recover sufficiently to allow a comeback.
"I would like to thank my family, Lancashire, England, all my sponsors, friends and advisers for all the help and support they have given me throughout my career.
"Last, but by no means least, I am indebted to the encouragement and support I have always received from England's magnificent supporters.
"I will now be taking a break before deciding which future direction to take."
Flintoff retired from Test cricket at the end of the 2009 Ashes series, having another knee operation two days later, while turning down the offer of a new central contract from the England and Wales Cricket Board.
However, he repeatedly expressed his desire "to be the best one-day player in the world" and underlined his continued commitment to his country for limited-overs matches.
Flintoff signed a new three-year contract with Lancashire in November 2009 while undergoing injury rehabilitation in Dubai but was forced to call off a planned comeback for the county's 2nd XI this summer.
Although he was named in Indian Premier League side Chennai Super Kings' provisional squad for the Champions League Twenty20 and his agent Andrew Chandler revealed that Flintoff was close to signing a deal to play domestic Twenty20 cricket for Queensland, fears grew that he might never represent England again.
In 79 Tests, he scored 3,845 runs at an average of 31.77, with five centuries - and although he captured 226 wickets at 32.78, he only took five wickets in an innings on three occasions.
Born in Preston, Flintoff made his reputation in schoolboy cricket as a hard-hitting right-hander and right-arm fast bowler and he made his Test debut against South Africa in July 1998 at the age of 20.
England had struggled for much of the 1990s as Australia became the pre-eminent power of the cricketing world, and Flintoff was the latest of a number of all-rounders weighed down under the expectation of being "the new Ian Botham".