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Adolescents who use a variety of cognitive and behavioral self-management strategies have been shown to report reduced rates of early-stage substance use, but little is known about how these personal competence skills may be protective. In a series of structural equation models, this study examined the association between competence skills and substance use over a 3-year period among 849 suburban junior high school students, and whether psychological distress, well-being, or both mediated this relation. Findings indicated that well-being fully mediated the relation between early competence and later substance use, but distress did not. Youth with good competence skills reported greater subsequent well-being, which in turn predicted less later substance use. Findings suggest that competence skills protect youth by enhancing well-being and that prevention programs should aim to enhance competence in order to promote resilience.