Sandridge Hill between Melksham and Bromham has been reopened after more than five hours following a serious crash.
The A3102 was closed after a head-on collision between a blue Vauxhall Corsa and a yellow pick-up truck shortly before 8am.
Police, ambulance and fire crews were on the scene, as well as the Wiltshire Air Ambulance, who treated the male car driver.
An Air Ambulance spokesman said: “We were sent to the scene as it came through to us as a very nasty accident.
“One patient was unconscious and trapped in his car, and the other was conscious. We dealt with the unconscious patient who was cut out of the car and anesthetised at the scene by a critical care doctor.”
The driver, believed to be a man in his late teens, was taken to Frenchay Hospital with head and possible pelvic injuries.
Police investigations continued until 12.30pm when Wiltshire Council's highways team took over. The council confirmed the road had been reopened shortly before 2pm.
Any witnesses to the crash are asked to contact Wiltshire Police on 101.