This research examined the hypothesis that religiosity buffers the impact of life stress on adolescent substance use. Data were from a sample of 1,182 participants surveyed on 4 occasions between 7th grade (mean age = 12.4 years) and 10th grade. Religiosity was indexed by Jessor's Value on Religion Scale (R. Jessor & S. L. Jessor, 1977). Zero-order correlations showed religiosity inversely related to alcohol, tobacco, and marijuana use. Significant Life Events x Religiosity buffer interactions were found in cross-sectional analyses for tobacco, alcohol, and marijuana use. A latent growth analysis showed that religiosity reduced the impact of life stress on initial level of substance use and on rate of growth in substance use over time. Implications for further research on religiosity and substance use are discussed.