This article reports adolescent substance use outcomes of universal family and school preventive interventions 5(1/2) years past baseline. Participants were 1677 7th grade students from schools (N=36) randomly assigned to the school-based Life Skills Training plus the Strengthening Families Program: For Parents and Youth 10-14 (LST+SFP 10-14), LST-alone, or a control condition. Self-reports were collected at baseline, 6 months later following the interventions, then yearly through the 12th grade. Measures included initiation-alcohol, cigarette, marijuana, and drunkenness, along with a Substance Initiation Index (SII)-and measures of more serious use-frequency of alcohol, cigarette, and marijuana use, drunkenness frequency, monthly poly-substance use, and advanced poly-substance use. Analyses ruled out differential attrition. For all substance initiation outcomes, one or both intervention groups showed significant, positive point-in-time differences at 12th grade and/or significant growth trajectory outcomes when compared with the control group. Although no main effects for the more serious substance use outcomes were observed, a higher-risk subsample demonstrated significant, positive 12th grade point-in-time and/or growth trajectory outcomes for one or both intervention groups on all measures. The observed pattern of results likely reflects a combination of predispositions of the higher-risk subsample, the timing of the interventions, and baseline differences between experimental conditions favoring the control group.