The two men were airlifted to the Edinburgh Royal Infirmary while a family of three were taken by ambulance following the collision yesterday.
One paramedic was on the scene in under five minutes and battled to save one man's life until a helicopter arrived, while firefighters put out a blaze in one of the cars.
A woman, believed to have minor injuries, was taken to Wishaw General, while a vet was called to treat an dog injured in the crash.
Police closed the road following the incident near to Polkemmet Country Park in Whitburn around 3:30pm.
A spokeswoman for the ambulance service said: "We had one paramedic on the scene within five minutes of the collision and the Medic One trauma team were requested from the ERI.
"One male patient was critical and another had serious injuries. We requested a helicopter from RAF Prestwick to transport them to the ERI and they arrived there around 4:30pm.
"The closest hospital was Wishaw General but due to the nature of the injuries they were taken to Edinburgh.
"One male and two female casualties, which I believe were a family, were taken in one ambulance to the ERI, with relatively minor injuries while another female casualty was taken to Wishaw General, it would seem with minor injuries.
"A vet was also requested for an injured dog, who was taken to a local clinic to be treated."
A spokeswoman for the fire service confirmed a fire had been extinguished in one of the cars while a spokeswoman for the police said the road had been closed to allow officers to investigate the incident.