The Trans-Canada Highway, east of Calgary, was shut down for a number of hours after two vehicles collided head-on in the westbound lanes.
Officials say they were called to the scene of the crash at around 11:00 p.m. on Wednesday.
The crash involved a truck and an SUV and police say one of the vehicles was driving the wrong way down the road.
The male drivers of both vehicles, a 27-year-old from Chestermere and a 30-year-old from Calgary, were declared dead at the scene.
The incident resulted in the closure of the westbound lanes of the route, but that order has since been lifted.
RCMP is investigating.
