Doubts have been cast over the future of St Bartholomew's (Barts) hospital after the Government called for a review of redevelopment plans.
The Royal London will become the UK's biggest new hospital
Work has already begun on a £1.3bn Private Finance Initiative (PFI) scheme to rebuild both Barts and the Royal London Hospital.
But the Department of Health (DoH) says Barts inclusion should be reconsidered to ensure it is "affordable".
The Trust says it is and both buildings are in need of refurbishment.
Under the scheme the Royal London would have been the UK's biggest new hospital and Barts would have got a state-of-the-art Cancer and Cardiac Centre of Excellence.
The plans are thought to have achieved one of the biggest NHS funding deals in recent years.
A statement from the DoH said: "We have asked the trust to re-consider its plans to ensure that the Barts and Royal London scheme is both affordable and meets local needs.
"The trust has been asked to consider further the inclusion of the Barts element within the scheme as part of this process.
"The department and local NHS remain committed to delivering the necessary improvements to health services in this part of London and hope to agree a way forward in the near future."
But a statement from the Barts and The London NHS Trust said the two hospitals facilities desperately needed to be replaced.
It said: "The long-anticipated and much-needed redevelopment of both hospitals will deliver world-class medical facilities for the people of East London and beyond, including 300,000 new Thames Gateway residents.
This project is affordable. It will also deliver value for money."