An air ambulance was called to the scene of a serious collision near Boroughbridge.
It happened last night, Thursday on the A168 at 5.38pm.
Four vehicles were involved including a Golf, a Land Rover and trailer, Mini and a Volvo.
The Great North Air Ambulance Service (GNAAS) attended along with other emergency vehicles.
The driver of the Golf, a man in his 70s was taken to Leeds General Infirmary with serious leg injuries, the driver of the Mini, a 19-year-old woman was taken to LGI with serious head injuries, a passenger in the Mini, a woman in her fifties, was also taken to hospital with serious leg and hand injuries.
The occupants of the Land Rover and Volvo were uninjured.
North Yorkshire Fire and Rescue Service say they had to cut three people out of vehicles.
The road was closed to allow emergency services to tend to the casualties and for collision investigators to examine the scene.
It reopened at around 1.30am in the early hours.
Any witnesses to the collision are asked to call North Yorkshire Police on 101.
Please quote reference 1216015908.