Five people in total were taken to hospital following the crash on the A71 on the outskirts of Edinburgh on Tuesday.
The collision happened at around 1.30pm, west of the junction with Dalmahoy Road.
Police Scotland said a westbound Renault flatbed truck hit a grey Renault Clio travelling in the other direction. The truck then collided head-on with a grey Volvo XC60.
The Volvo driver and his female passenger, both aged 70, were taken to Edinburgh Royal Infirmary (ERI) with serious injuries. Their injuries are not thought to be life-threatening.
The 87-year-old driver of the Renault and his 85-year-old female passenger were also taken to the hospital with minor injuries, as was the 56-year-old man driving the truck.
The road was closed for around 10 hours while investigations were conducted at the scene.
Appealing for witnesses, Sergeant Kos Papakyriakou said: “Those travelling in the Volvo were seriously injured, however, thankfully, their injuries are not believed to be life-threatening.
“As part of our inquiries we’d urge anyone who witnessed this collision, and who has not yet spoken to officers, to get in touch with us.
“We’d also ask anyone who may have seen any of the vehicles beforehand, or has information which may be able to help, to come forward.”
Anyone with information can contact Police Scotland on 101.