Transportation is essential to the economic development of Mato Grosso State, Brazil, and Federal Highway 163 is the main route for marketing regional agricultural produce. One unfortunate consequence of this activity is the occurrence of motor vehicle accidents. With the aim of analyzing and categorizing the main factors associated with motor vehicle accidents on this highway, the current study used data from the Mato Grosso State Division of the Brazilian Federal Highway Patrol for the year 2004. Factors significantly associated with accidents involving casualties were: substandard paving (OR = 1.89; CI: 1.32-2.70); front-end collisions (OR = 14.14; CI: 8.96-22.32); and running over pedestrians (OR = 35.95; CI: 8.10-159.52. Contributing factors included highway maintenance problems (OR = 4.35; CI: 1.94-9.75) and disobeying traffic signs (OR = 5.69; CI: 2.01-16.12). In conclusion, reduction of motor vehicle accidents on this highway requires comprehensive intervention rather than targeting measures only to drivers or highway patrol personnel, but considering regional issues and their economic, social, and cultural dimensions.