This study investigated the relationship between academic factors and past-year alcohol, cigarette, and marijuana use in an adolescent sample of Latinos. Secondary data analysis was conducted using a subsample of Latino adolescents (N = 2,593) from the 2006 National Survey on Drug Use and Health. School connectedness and parental involvement in school were protective across all substances. Fighting in school increased the risk for use of all substances, and failing grades increased the risk for alcohol and marijuana use. Implications for prevention include the development of prevention programs that aim to increase students' connection to school and increase parental involvement. (Published Abstract)