Literature on substance use and academic performance suggests, overall, that students’ use of alcohol, marijuana, or other illicit drugs has a negative effect on academic performance, but generally has not included the full range of substances or incorporated statistical controls in a single model. Using school-level data, multilevel regression analyses are performed to explore the relationship between the prevalence of substance use in a school and standardized test scores. Results suggest that substance use does not contribute to low performance and that low standardized test scores are more strongly correlated with social inequality and poverty in the school system.