Emergency department (ED) visits present an opportunity to deliver brief interventions to reduce violence and alcohol misuse among urban adolescents at risk of future injury. To determine the efficacy of brief interventions addressing violence and alcohol use among adolescents presenting to an urban ED. Between September 2006 and September 2009, 3338 patients aged 14 to 18 years presenting to a level I ED in Flint, Michigan, between 12 pm and 11 pm 7 days a week completed a computerized survey (43.5% male; 55.9% African American). Adolescents reporting past-year alcohol use and aggression were enrolled in a randomized controlled trial (SafERteens). All patients underwent a computerized baseline assessment and were randomized to a control group that received a brochure (n = 235) or a 35-minute brief intervention delivered by either a computer (n = 237) or therapist (n = 254) in the ED, with follow-up assessments at 3 and 6 months. Combining motivational interviewing with skills training, the brief intervention for violence and alcohol included review of goals, tailored feedback, decisional balance exercise, role plays, and referrals. Self-report measures included peer aggression and violence, violence consequences, alcohol use, binge drinking, and alcohol consequences. About 25% (n = 829) of screened patients had positive results for both alcohol and violence; 726 were randomized. Compared with controls, participants in the therapist intervention showed self-reported reductions in the occurrence of peer aggression (therapist, -34.3%; control, -16.4%; relative risk [RR], 0.74; 95% confidence interval [CI], 0.61-0.90), experience of peer violence (therapist, -10.4%; control, +4.7%; RR, 0.70; 95% CI, 0.52-0.95), and violence consequences (therapist, -30.4%; control, -13.0%; RR, 0.76; 95% CI, 0.64-0.90) at 3 months. At 6 months, participants in the therapist intervention showed self-reported reductions in alcohol consequences (therapist, -32.2%; control, -17.7%; odds ratio, 0.56; 95% CI, 0.34-0.91) compared with controls; participants in the computer intervention also showed self-reported reductions in alcohol consequences (computer, -29.1%; control, -17.7%; odds ratio, 0.57; 95% CI, 0.34-0.95). Among adolescents identified in the ED with self-reported alcohol use and aggression, a brief intervention resulted in a decrease in the prevalence of self-reported aggression and alcohol consequences. clinicaltrials.gov Identifier: NCT00251212.