Purpose We evaluate the efficacy of a short family intervention in reducing sexual risk behavior, drug use, and delinquent behaviors among homeless youth. Methods A randomized controlled trial of 151 families with a homeless adolescent aged 12 to 17 years. Adolescents were recruited from diverse sites in southern California from March 2006 through June 2009 and assessed at recruitment (baseline), 3, 6, and 12 months later. Families were randomly assigned to an intervention condition with five weekly home-based intervention sessions or a control condition (standard care). Main outcome measures reflect self-reported sexual, substance use and delinquent behaviors over the last 90 days. Results Sexual risk (e.g., mean number of partners) (p < .001), alcohol use (p = .003), hard drug use (p < .001), and delinquent behaviors (p = .001) decreased significantly more over 12 months in the intervention condition compared to the control condition. Marijuana use, however, significantly increased in the intervention condition compared to the control condition (p < .001). Conclusion An intervention to re-engage families of homeless youth has significant benefits in reducing risk over 12 months.