Police were called to reports of a collision at the junction of Waterloo Road and Shawbridge Street at around 6.15pm on Saturday (April 25).
A Vauxhall Astra travelling southbound collided with a Volkswagen Polo before striking a Ford Kuga car travelling northbound.
A passenger in the Vauxhall, a 32-year-old man from Great Harwood, suffered a "dislocated fracture" to his ankle and foot.
He was taken to Royal Blackburn Hospital for treatment.
Police are now appealing for witnesses to establish exactly what happened.
Sgt Mick Belfield, of Lancashire Police’s Tactical Operations team, said: "We are appealing for witnesses after a road traffic collision in Clitheroe.
"A man has been left with a serious lower leg injury and we want to establish the exact circumstances.
"If you have any information please come forward.”
The driver of the Vauxhall, a 21-year-old man, sustained a cut to his knee.
The driver of the Volkswagen, a 17-year-old girl, and the driver of the Ford, a 39-year-old man, both suffered minor injuries.
The road was closed for four hours while accident investigators attended the scene.
Anyone with information should contact police by calling 101 or emailing [email protected], quoting log 1297 of April 25.