Two men have died following the crash involving a double decker bus and a lorry on the A47 in Wisbech, Cambridgeshire Police said.
Emergency crews were called to the A47 in Wisbech at around 7.30am on Tuesday and pictures showed a bus had smashed into the side of a lorry.
The two men were passengers on the bus at the time of the collision, Cambridgeshire Police said. Seven others have been seriously injured and 11 people have minor injuries, the force spokesman added.
Sixteen patients were transferred to hospital following the incident at Thorney Road in Guyhirn, the East of England Ambulance Service said.
Police officers were still at the scene this morning and warned drivers the road would be closed "for some time".
The East of England Ambulance service initially declared it as a "major incident" because of the number of patients involved, but were stood down at 9.50am.
In a tweet the Magpas Air Ambulance charity said: "Magpas-Charity enhanced doctor and paramedic team were called to a major incident on the A47 in the Wisbech area, involving an HGV and a bus.
"Approximately 15 people have been injured. All emergency services are on the scene. More info to come."
East of England Ambulance Service said it had sent seven ambulance crews, three ambulance officers, two rapid response vehicles, and a Hazardous Area Response Team (HART) to the scene.
Cambridgeshire Fire Service said crews were called at 7.33am.