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Objective: Driving under the influence of alcohol or drugs is a risk factor for motor vehicle accidents (MVAs). This issue has become an increasing concern for the governments of many European and North American countries, thereby encouraging the adoption of preventive policies. The aim of this study was to investigate the associations between major clinical outcomes and alcohol or drug abuse among drivers involved in MVAs who were referred to an Italian Emergency Department., Patients and Methods: The study population consisted of consecutive injured drivers who were admitted to the Emergency Department following an MVA during a period of one year. The patients' blood alcohol concentrations (BACs) and the presence of the most common drugs of abuse [amphetamine, methamphetamine, methylenedioxymethamphetamine (MDMA), barbiturates, benzodiazepines, benzoylecgonine (cocaine main metabolite), cannabinoids, methadone, and opiates)] were determined and evaluated in association with major clinical outcomes and demographic data., Results: Overall, 347 injured drivers were enrolled. Of the 347 enrolled patients, 164 (47.3%) had a positive BAC (greater than 5 mg/dL). A subgroup of 107 injured drivers was also screened for drugs of abuse. Thirty-seven of these subjects (34.5%) were positive for at least one drug. A statistically significant association was found between BAC and triage at admission (p<0.01), hospitalization (p<0.01), and lesions of internal organs (p=0.04)., Conclusions: The results of this study show that a significant proportion of injured drivers had detectable levels of BAC and/or illegal drugs. Positive BACs were significantly associated with worse clinical outcomes. These findings suggest that the implementation of methods to prevent alcohol and drug abuse is of paramount importance in the effort to reduce the rates of MVAs and their dramatic consequences.