The dead are two female rear seat passengers and the male driver of the van, Constable Greg Nolet of Wanaka said.
A fourth man from the van was flown to Dunedin Hospital by the Otago Regional Rescue helicopter, a St John spokesman said the patient had serious injuries including possible leg injuries.
The driver of the truck and trailer unit was uninjured but shaken by the accident.
The crash occurred at the intersection of State Highway 8A (Shortcut Road) and State Highway 6 when a truck and van collided at 4.35pm this afternoon.
A detour remains in place.
Full details in tomorrows' Otago Daily Times