Barts and The London NHS Trust is to cut 635 jobs over the next two years as it tries to reduce costs.
There are expected to be 200 compulsory job losses but the trust said it hoped the rest would be covered by voluntary redundancies and other departures.
Nearly 10% of nursing posts and 100 beds will go and there will be 290 fewer corporate and back-office roles.
The decision was branded “a disgrace” by the Unison union and “outrageous” by the Royal College of Nursing.
The trust includes Barts in the City, the Royal London in Whitechapel and the London Chest Hospital in Bethnal Green.
About 100 beds will go and nearly 260 nursing posts will be lost, or 10% of the total.
Some nurses will be replaced by healthcare assistants, who are cheaper to employ.
Dr Peter Carter, chief executive of the Royal College of Nursing, said it was “outrageous that such a large number of staff could be lost from the frontline”.
“The idea that such a thing could be done without seriously jeopardising patient care is ludicrous,” he said.
“How on earth do they think that hospitals and community services are going to cope?”
There will also be 83 fewer clinical and diagnostic posts, with 220 fewer administrative and clerical posts and 72 corporate roles being closed.
The total saving from the job losses is expected to be £30m.
A statement from the trust said it had reviewed every aspect of its expenditure to ensure it was “truly essential and represents best value”.
“By changing the way we work, we can reduce our staffing levels at the same time as improving quality”, it said.
“We do not expect any compulsory redundancies among frontline clinical staff.”
But Karen Jennings, the head of health at Unison, said patient care “will suffer when nurses disappear from wards, waiting lists creep up and the agony of bed shortages returns”.
“Cutting administrators is a huge mistake and will only mean other staff such as nurses have to pick up the pieces,” she said.