An England and Wales Cricket Board (ECB) statement Thursday said the operation, the fourth on the Yorkshire batsman's right knee, would mean Vaughan would be out of cricket for a period of four to six months.
"Michael worked extremely hard with the support of the Yorkshire medical staff to strengthen the knee to the point where he was able to begin playing again," said ECB chief medical officer Dr Peter Gregory.
"However, he has still been experiencing some discomfort in the knee and further surgery is necessary if he is to regain the level of fitness required for international cricket."
It now seems as if only an extraordinary recovery would allow Vaughan, who led England to a 2-1 home success against Australia last year, to take part in his team's defence of the Ashes when the series starts in November.
The news that their 31-year-old captain is to have yet more surgery will come as a huge blow to England, whose Test series triumph over Australia last year was their first since 1986/87.
Vaughan has not played for England since being forced home early from the tour of India in March and last week his knee injury flared up again during Yorkshire's County Championship match away to Sussex at Arundel, where he was unable to field for much of the game.
That led him to see a new specialist Thursday where it was decided he needed an operation to repair damage to the articular cartilage in his right knee.
Confirmation of Vaughan's extended absence has now left the England selectors with the dilemma of finding a new permanent captain.
"Our priority now is to safeguard Michael's long-term interests and ensure that he can resume his playing career," added Gregory.
"He will have our full support and we will be closely monitoring his progress in conjunction with the staff at Yorkshire who will supervise his day-to-day rehabilitation programme."
England coach Duncan Fletcher added: "I really feel for Michael. He is so keen and passionate about playing for England and really wants to get out there and score runs for us again.
"There was no messing around for him, he did everything properly and it's desperately bad luck that he now has to have an operation.
"He just loves batting and scoring runs and to have that taken away must be very hard for him.
"He is desperate to get back playing again and we all are hoping the operation is successful and he can return for England."
Although the first Ashes Test is not due to start at Brisbane until November 23, England will want Vaughan, who will have hardly played in a year by then, to come through several matches before recalling him for international duty.
They could name Vaughan in their squad in the hope he is fit for Tests later in the five-match series but his chances of featuring at Brisbane's Gabba ground now look remote.
Assuming his rehabilitation works out as planned, Vaughan could feature at next year's World Cup in the West Indies as England's opening match, against New Zealand, is not until March 16.
He is one of several senior players on England's sick list with all-rounder Andrew Flintoff (ankle), left-arm spinner Ashley Giles (hip), fast bowlers Simon Jones (knee) and James Anderson (back) also ruled out of the ongoing one-day series with Sri Lanka, where batsman Kevin Pietersen (knee) and Paul Collingwood (thigh) were the latest to sustain injuries.
Flintoff, Andrew Strauss and Marcus Trescothick have all filled in while Vaughan has been sidelined and, while they remain the leading candidates to take over, all have had their captaincy credentials called into question.
Fletcher insisted a decision on the leadership had still to be taken ahead of next month's first of four Tests against Pakistan at Lord's.
"We will decide as a selection panel about who captains the team for the rest of the summer. From my point of view I just want the best person for the team and we'll be deciding that before the first Test."