The incident happened shortly after 8 a.m. PT when a motorcycle travelling south on Burrard Street struck the car that was eastbound through the intersection with West 2nd Avenue, according to Vancouver police Const. Brian Montague.
Both of the motorcycle riders, a 22-year-old woman and a man whose age is not yet known, died from their injuries. Police have not released the identities of the victims.
The driver of the car was taken to hospital with minor injuries.
Burrard Street is expected to remain closed between 1st and 3rd avenues for several hours while the Vancouver Police Collision Investigation Unit investigating the collision.
The deaths were Vancouver's 15th and 16th traffic fatalities of 2012.