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Abstract: Aims: To describe the prevalence of recent use of alcohol, medication, and illegal drugs among patients who attended emergency departments (EDs) as a result of suffering an injury due to any external mechanism and to identify factors associated with alcohol and drug use. Methods: A cross-sectional study was conducted in eight university hospitals in Spain. Participants were adult patients admitted to a trauma ED. Oral fluid was used to test for psychoactive substances analyzed by gas chromatography–mass spectrometry. Socio-demographic data and information on circumstances of the injury were collected through interviews. Results: The analysis included 1579 patients admitted to the EDs (56.4% men). Among young people (<40 years), 21.4% of men and 8.5% of women were positive for any illegal substance, primarily cannabinoids or cocaine; 24.7% of men and 14.8% of women were positive for alcohol. Among patients ≥40 years, 7.4% of men and 1.6% of women were positive for any illegal substance, and 16.3% and 11.0% respectively for alcohol. Prevalence of substance detected varied across mechanism of injury, gender and age group. Night-time injury was associated with substance use. Conclusions: A high proportion of injured patients who were treated in an EDs tested positive for psychoactive drugs. Routine testing at trauma departments would maximize the identification of patients who may benefit from referral to specialized addiction treatment centers, or brief interventions. [Copyright &y& Elsevier]