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A substantial number of trauma center admissions are related to driving under the influence (DUI); however, there has been no prior report of brief intervention (BI) after injury reducing subsequent DUI arrests. The hypothesis of this study was that injured patients receiving BI would have a lower risk of DUI arrest within 3 years of discharge than those receiving standard care (SC).This prospective, randomized clinical trial randomly allocated patients involved in motor vehicle collisions to receive SC or a BI regarding alcohol use. The primary outcome measure was DUI arrest within 3 years of hospital discharge. DUI arrests were documented by matching demographic information to state traffic safety data.After randomization (N = 126), BI and SC groups were similar in age, prior DUI arrests, and alcohol screening score. BI sessions lasted an average of 30 minutes and were performed by either a social worker or a trauma surgeon. Approximately one in six participants (n = 21, 16.7%) had a DUI arrest within 3 years of hospital discharge. Within 3 years of hospital discharge, 14 of 64 patients (21.9%) in the SC group had an arrest for DUI compared with only 7 of 62 patients (11.3%) who received the BI. Multivariate analysis demonstrated that BI was the strongest protective factor against DUI arrest (odds ratio [OR], 0.32; 95% confidence interval ≤CI], 0.11–0.96). Prior number of DUIs (OR, 1.43; 95% CI, 1.03–2.01) and age (OR, 0.94; 95% CI, 0.88–0.99) were also associated with DUI arrest posthospitalization, but alcohol screening score (OR, 1.06; 95% CI, 0.99–1.13) was not. The absolute risk reduction implies that only nine patients would need to receive a BI to prevent one DUI arrest.Patients who receive BI during a trauma center admission are less likely to be arrested for DUI within 3 years of discharge. BI represents a viable intervention to reduce DUI after trauma center admission.