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This study evaluated the substance initiation effects of an intervention combining family and school-based competency-training intervention components. Thirty-six rural schools were randomly assigned to 1 of 3 conditions: (a) the classroom-based Life Skills Training (LST) and the Strengthening Families Program: For Parents and Children 10–14, (b) LST only, or (c) a control condition. Outcomes were examined 1 year after the intervention posttest, using a substance initiation index (SII) measuring lifetime use of alcohol, cigarettes, and marijuana and by rates of each individual substance. Planned intervention-control contrasts showed significant effects for both the combined and LST-only interventions on the SII and on marijuana initiation. Relative reduction rates for alcohol initiation were 30.0% for the combined intervention and 4.1% for LST only.