Up to 1,000 jobs could be lost at a Greater Manchester NHS trust as it tries to save millions of pounds by April 2012.
The Pennine Acute Trust runs North Manchester General, Fairfield in Bury, Rochdale Infirmary and the Royal Oldham Hospital and employs 10,000 staff.
It expects to have to save £45m but said that could rise once it knows the services GPs want to commission.
Chief executive John Saxby said he hoped to avoid compulsory redundancies.
Mr Saxby said the trust faced an "unprecedented" financial challenge and savings could not be achieved purely by cutting waste and other expenditure.
"I believe it is right for the trust to consider all options in its efforts to reduce costs and work more efficiently so we can provide safe, high-quality, reliable and sustainable services through this economic downturn and beyond," he said.
"Around 70% of our expenditure is on staffing costs.
"We are, therefore, informing our trade unions of our need to reduce posts across the trust by a significant number during 2011-12 and we are also affirming our commitment to work through the impact of that with them."
He said the trust, which serves a population of about 800,000, still had a "reasonable level of natural turnover of staff" and managers would be looking to redeploy permanent staff into any vacancies.
Permanent staff would also be moved into posts currently covered by temporary employees, and overtime will be reduced.
"I sincerely expect that at the end of this process everyone who wishes to continue to work for the trust will still be with us," Mr Saxby added.