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The short-term results of a randomized trial testing a brief feedback and motivational intervention for substance use among homeless adolescents are presented. Homeless adolescents ages 14–19 (N = 285) recruited from drop-in centers at agencies and from street intercept were randomly assigned to either a brief motivational enhancement (ME) group or 1 of 2 control groups. The 1-session motivational intervention presented personal feedback about patterns of risks related to alcohol or substance use in a style consistent with motivational interviewing. Follow-up interviews were conducted at 1 and 3 months postintervention. Youths who received the motivational intervention reported reduced illicit drug use other than marijuana at 1-month follow-up compared with youths in the control groups. Treatment effects were not found with respect to alcohol or marijuana. Post hoc analyses within the ME group suggested that those who were rated as more engaged and more likely to benefit showed greater drug use reduction than did those rated as less engaged. Limitations of the study are discussed as are implications for development of future substance use interventions for this high-risk group.