A company which became the first private firm to manage an NHS hospital says it wants to "withdraw from its contract".
Circle Holdings, which operates Hinchingbrooke Hospital in Cambridgeshire, said its franchise is "no longer viable under current terms".
The move comes amid funding cuts and pressure on the casualty department, Circle said.
The Department of Health said it was "disappointed" in the decision.
Circle took on Hinchingbrooke in early 2012, as it faced closure.
'Unsustainable'It said there had been unprecedented increases in accident and emergency attendances, a lack of care places for patients awaiting discharge, and that funding had been cut by 10.1% this financial year.
Circle has made payments to the trust totalling about £4.84m and could be required to make a final support payment of approximately £160,000, the firm said.
Under the terms of its 10-year contract, it has the right to end the franchise if the amount of money it has to put in to the trust exceeds £5m.
Chief Executive Steve Melton said: "This combination of factors means we have now reluctantly concluded that, in its existing form, Circle's involvement in Hinchingbrooke is unsustainable."
Circle chairman Michael Kirkwood said the decision had been made "with regret and after considerable thought".
The health watchdog, the Care Quality Commission, recently carried out an inspection of Hinchingbrooke Hospital and said it would publish its findings later.
AnalysisBy Nick Triggle, BBC health correspondent
Circle has quickly looked to place the blame on the way things have worked out with Hinchingbrooke Hospital on the current conditions in the NHS, citing rising A&E attendances and the squeeze on funding.
Those issues have almost certainly had a role to play in the decision to pull out of the contract.
But there is undoubtedly more to it than that - after all the current pressures have not just appeared from nowhere. They were building when the idea of the contract started being discussed in 2009.
When Circle took over, there were question marks over whether the firm was being too ambitious in claiming it could turn the hospital around.
Hinchingbrooke had been called a "basket case" with historic debts of nearly £40m.
Within six months of Circle taking over, losses were twice what was forecast. However, as time went by improvements to services were made.
But still they could not escape the past. The Care Quality Commission has just carried out an inspection of the hospital.
It is yet to be published, but Circle knows the contents. It is widely expected to be critical.
The GMB Union said the Circle takeover had been the "disaster waiting to happen when you get the private sector involved in running a hospital".
Spokesman Steve Sweeney said: "It's not overly surprising to see them try to pack their bags, cut loose and walk away.
"Obviously having the major backers walk away leaves [the hospital] in a very vulnerable position .... we're hoping that there's some planning in place to aid and assist that."
A spokesman for the Department of Health said: "There will now be a "managed transfer of the running of the trust and patient care will not be affected."
Jonathan Djanogly, Conservative MP for Huntingdon, said the way these contracts are issued "needs to be looked at".
"I think probably Circle was too aggressive in terms of its pricing, but at the same time the NHS made Circle take all of the debts of the previous incarnation of the hospital," he said.
Andy Burnham, the shadow health secretary, said: "Patients who rely on Hinchingbrooke will be worried about their hospital following this announcement.
"It was the decision of the coalition in November 2011 to appoint Circle and they must take responsibility for this mess.
"The government were explicitly warned two years ago about the risky business model Circle were operating, but failed to take any action."
The company claimed it "remains a committed partner of the NHS at our elective treatment centres and independent hospitals", adding it is in discussion with the NHS Trust Development Authority to ensure an "orderly withdrawal".
Circle runs private hospitals in Bath and Reading, which both accept NHS patients, and it also has NHS treatment centres in Bedfordshire and Nottingham.
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