The road was closed for six hours following the collision that was near to the Kex Gill farm.
The collision involved a blue Volkswagen Bora travelling from Skipton towards Harrogate and a black Ford C-max people carrier heading in the opposite direction.
The driver of the Volkswagen, a 58-year-old man from Silsden, West Yorkshire, was taken to Leeds General Infirmary by air ambulance with serious injuries, where he currently remains. The occupants of the C-max, two women and a boy from Harrogate, were taken to Harrogate District Hospital with non life-threatening injuries.
Traffic Sergeant Andrew Morton, Force’s Roads Policing Group, said: If you were in the area of the A59 at the time of the collision, I urge you to contact the police straight away as you may have vital information which could help this investigation.
I am also keen to speak to anyone who may have seen either of the vehicles prior to the incident and ask them to get in touch as soon as possible.
Anyone who can assist with this enquiry should contact Harrogate police on 101, select option 2 and ask for Chris Dundon. Alternatively, information can be emailed to firstname.lastname@example.org
Please quote reference number 12140029210.