Several wards at Altnagelvin Hospital in County Londonderry have been evacuated due to a fire at the top of the 11-storey building.
Almost 50 firefighters and 11 fire appliances are at the scene. The police are also in attendance.
The Western Health Trust has reassured the public that "there are no injuries and the incident is under control".
It has set up helpline numbers for anyone concerned about the fire. They are 028 7129 6202 and 028 7129 6204.
The hospital consultant in charge of the evacuation, Alan McKinney, said the operation had been treated as "a major incident" and the first priority was patient safety.
"When we discovered that there was a fire in the top of the tower block, and water damage coming through to our wards, the decision was made to move all of our patients to safe, comfortable locations elsewhere on the trust's site," Mr McKinney said.
The Northern Ireland Ambulance Service (NIAS) said it had "declared a major incident" at 19:34 GMT on Friday, following reports of a fire at the hospital and "the potential requirement to move large numbers of patients".
It added that hospitals throughout Northern Ireland and County Donegal were informed and stood "ready to receive patients if necessary".
In a statement, NIAS said it had been alerted that, although the fire was "contained within a relatively small area, other wards had been affected by smoke and water damage".
Speaking from the scene, Mark H Durkan from the SDLP said it had been a "chaotic evening" and there were "emergency vehicles of all types all over the hospital grounds".
He added that it appeared that calm was gradually being restored.
The MLA said he had been speaking to senior management at Altnagelvin and it was his understanding that the fire broke out on the roof, where water tanks are stored.
"Whatever happened - these tanks collapsed or burst - and that water has come down...through the roof and through ceilings and floors," he said.
Mr Durkan said he understood that that water had passed down from the tenth floor to the third floor - leading to the evacuation of all eight affected wards.
The Western Health Trust said firefighters, police and ambulance staff assisted with the evacuation of a number of wards and Translink buses were used in the operation.
The trust added: "Patients in the affected wards are being transported to appropriate hospital or other care settings."
It has advised visitors not to come to Altnagelvin until further notice.
The entrances to the hospital have been closed to all non-emergency personnel.
The Mayor of Derry, Sinn Féin Councillor Kevin Campbell has paid tribute to "all the emergency services who worked together to ensure the safety of staff and patients at the hospital".
"While the emergency service practice for these occasions, tonight's actions highlight their true professionalism and teamwork under real conditions," Mr Campbell added.
Just over two weeks ago, two wards in Altnagelvin were evacuated after a small fire broke out in an electrical switch room.
Twenty patients were moved to other parts of the hospital while 30 firefighters brought the blaze under control on 6 November.