The accident and emergency unit at the birthplace of the NHS will be axed, Health Secretary Jeremy Hunt has confirmed.
Campaigners have fiercely opposed the closure of the A&E unit at Trafford General Hospital in Manchester.
But following a review of the plan by the Independent Reconfiguration Panel (IRP), Mr Hunt confirmed that the closure can go ahead - provided that nearby A&E departments consistently meet national waiting time targets.
The minister told the House of Commons that changes are "necessary to provide safe and sustainable healthcare in the North West". Health bosses in the region said the way services are delivered in Trafford and Manchester needs to be fundamentally changed.
The plans involve the removal of A&E services at Trafford General between midnight and 8am, and for the rest of the time the unit will be downgraded to an urgent care centre. It will eventually be downgraded to a minor injuries unit. Emergency surgery will no longer be provided at the site and the intensive care unit will shut.
Campaign group Save Trafford General has said the move makes "no sense". Local councillors also appealed to Mr Hunt to review the decision, saying they were concerned the plans were "principally financially motivated" and could put pressure on other hospital sites.
Mr Hunt referred the matter to the IRP, which concluded that the "clinical case for change is clear", MPs heard. Health bosses said the hospital has the second smallest A&E department in the country, with an average of six to 12 people using the service between midnight and 8am.
Last week celebrations were held at the hospital to mark the 65th anniversary of the NHS. Trafford General is known as the birthplace of the health service as it treated the first NHS patient in 1948.
Matthew Finnegan, chair of the Save Trafford General campaign, said: "It is tearing the heart out of the hospital - the birthplace of the NHS - and that means that the hospital's future is in real danger. It will mean that patients will have to travel further and wait longer for treatment."
Mr Hunt also announced that planned changes to vascular services in Cumbria and Lancashire should proceed. Services in the region will now be housed in three specialist centres at North Cumbria University Hospital NHS Trust in Carlisle, East Lancashire Hospitals NHS Foundation Trust in Blackburn, and Lancashire Teaching Hospitals NHS Foundation Trust in Preston.
Mr Hunt told MPs: "Our primary objective as a Government must be for the NHS to provide the best service for patients. Sometimes that means making difficult decisions.
"Both of the decisions I am announcing today fall into that category. But both are necessary if we are going to provide safe and sustainable healthcare in the North West going forward."