A 25-year-old man was taken to Forth Valley Royal Hospital with significant injuries after the crash at the A985 Valleyfield at around 7am.
The road was closed from 7am until around 11.50am while investigations were carried out.
Traffic was diverted in both directions via the A977, amid major disruption to road users travelling between Fife and Edinburgh, as the Forth Road Bridge is closed until the New Year for structural repairs.
The collision involved a Vauxhall Astra travelling eastbound and a Peugeot Boxer travelling westbound.
The Scottish Ambulance Service also treated a 56-year-old man at the scene.
Temporary Road Policing Inspector Andrew Thomson said: “I want to thank road users for their patience while we conducted our enquiries and worked to reopen the road.
“Our enquiries continue and anyone with information about this collision is asked to contact Police Scotland on 101 or contact Crimestoppers anonymously on 0800 555 111.”