At least six people were killed when two buses collided in Tay Ninh Province early on Monday morning.
The collision occurred at 4 a.m., badly damaging both vehicles and injuring 10 other people, who have been rushed to a local hospital and another in Saigon, around two hours away.
Doctors said some of the cases were critical.
Survivors on the ill-fated bus said their driver had shown signs of sleepiness, according to media reports.
People in Tay Ninh's Duong Minh Chau District said they were awakened by a massive bang.
“I opened the door to a disaster scene," a witness said. "Many people were dead while others were screaming and crying.”
Police are investigating further.
Road crashes are a leading cause of deaths in Vietnam, killing almost one person every hour. Experts blame narrow highways, poorly maintained vehicles and drivers' disregard for road safety and traffic rules for most fatalities.