This study examined the long-term substance use outcomes of 2 brief interventions designed for general population families of young adolescents. Thirty-three public schools were randomly assigned to 3 conditions: the 5-session Preparing for the Drug Free Years Program, the 7-session Iowa Strengthening Families Program, and a minimal contact control condition. The pretest involved 667 6th graders and their families. Assessments included multiple measures of initiation and current use of alcohol, tobacco, and marijuana. Pretest data were collected in the 6th grade and the reported follow-up data were collected in the 10th grade. Significant intervention-control differences in initiation and current use were found for both interventions. It is concluded that brief family skills-training interventions designed for general populations have the potential to reduce adolescent substance use and thus have important public health implications.