The purpose of this research was to determine the incidence and prevalence of drug use, alcohol use, and the combination of drug and alcohol use among motor vehicle crash (MVC) victims admitted to a Level-1 trauma center. In a 90-day study, nearly two-thirds of trauma center admissions were victims of motor vehicle crashes. Blood and urine was collected from 168 MVC victims of whom 108 were identified as the driver in the crash. Toxicology results indicated that 65.7% of drivers tested positive for either commonly abused drugs or alcohol. More than half of the drivers tested positive for drugs (50.9%) other than alcohol, with one in four drivers testing positive for marijuana use. About one-third of those using drugs had also been drinking, but alcohol was detected in only 30.6% of all injured drivers. Within the total MVC patient pool, passenger drug/alcohol use was equivalent to the driver population; however, injured pedestrians had higher rates of alcohol only than other MVC victims. There were no significant differences in drug and alcohol use between MVCs and trauma admissions of other causes. Of the patients with positive toxicology results, less than half (42%) were referred for evaluation for substance abuse disorders.