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This study tested the prediction that self-control would have buffering effects for adolescent substance use (tobacco, alcohol, and marijuana) with regard to 3 risk factors: family life events, adolescent life events, and peer substance use. Participants were a sample of public school students (N = 1,767) who were surveyed at 4 yearly intervals between 6th grade and 9th grade. Good self-control was assessed with multiple indicators (e.g., planning and problem solving). Results showed that the impact of all 3 risk factors on substance use was reduced among persons with higher scores on good self-control. Buffering was found in cross-sectional analyses with multiple regression and in longitudinal analyses in a latent growth model with time-varying covariates. Implications for addressing self-control in prevention programs are discussed.