In all, five people suffered injuries in the three-vehicle crash at Kawarau Bridge on the Gibbston Highway (State Highway6), about 11.45am on Saturday, a police spokeswoman said.
The road was blocked in both directions for about two and a-half hours while emergency services worked at the scene.
A Hato Hone St John spokesman said two people were seriously injured, one suffered moderate injuries and two more had minor injuries.
The two seriously injured patients were flown to Dunedin Hospital, while the others were either treated at the scene or taken by ambulance to Lakes District Hospital.
A Fire and Emergency NZ spokesman said three people were trapped when firefighters first arrived.
Crews from Frankton, Arrowtown and Queenstown responded.
A 50kmh temporary speed restriction was in place once the bridge reopened on Saturday afternoon.
The police serious crash unit was advised of the incident.
