This study examined self-reported substance use in relation to social capital and residential mobility by administering a survey to high school students attending three Midwestern schools. The results of this study provide partial support for social capital theory. Pearson’s correlations indicate a relationship between residential mobility and two social capital variables, community involvement and community support. Results from binary logistic regression and linear regression find that students with higher levels of family and school social capital report lower levels of substance use, and higher levels of peer support are related to higher levels of reported substance use. Further exploration of interactions between social capital measures and residential mobility finds that peer support suppresses the other social capital variables in relation to substance use. Although little support was found for residential mobility, other variables found to be significant with social capital and substance use include immigration status and grade.