A man was trapped in a car following a two-car collision on Clutha Valley Rd, about 5km from Balclutha, shortly before 4pm.
Ambulance, police and fire staff were called to the scene and traffic was diverted.
A spokeswoman for St John said two patients received moderate injuries and were taken to Clutha Health First for medical treatment.
The crash closed Clutha Valley Rd for an hour while the man was cut free, and the vehicles removed.
