The three-vehicle crash happened outside the rear entrance to Floors Castle in Kelso.
The crash happened on the B6397, on Friday afternoon just before 3.30pm, with police, paramedics and firefighters rushing to the scene.
The 60-year-old driver of a Fiat Ducanto van and the 56-year-old driver of a Vauxhall Combo van are both said to be in 'critical' conditions in the Borders General Hospital.
A 60-year-old woman who was a passenger in the Combo van was also badly hurt and was hospitalised.
A Land Rover Defender was also involved in the crash, but the 72-year-old man driving the car was unhurt as was the 53-year-old woman travelling with him.
Constable Leigh Rankine from the Road Policing Unit at Galashiels Police station said: "This has been a very serious collision, which resulted in significant injury to a number of individuals and we are eager to understand all of the factors, which contributed to this incident taking place.
"Any motorists who were on the road on Friday afternoon and witnessed what happened, should contact police immediately.
"Likewise, we would be extremely eager to obtain any relevant dash-cam footage the public may have of the collision, which can assist with our ongoing investigation."