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The current study examined longitudinal associations between friend’s substance use, friendship quality, parent-adolescent relationship quality and subsequent substance use. Participants were 166 adolescents, their parents and their close same-sex friends. Measures of relationship characteristics in the 10th grade were used to predict concurrent substance use and changes in substance use over a one-year period. The most consistent predictor of the use of different substances and changes in substance use over time was the friend’s substance using behavior. Negative interactions with a friend were related only to tobacco use, and friendship support neither contributed to nor protected against substance use. Mother-adolescent relationship support was associated with lower levels of concurrent substance use, as well as lower levels of hard drug use over time. Findings highlight the need to examine parents and peers simultaneously and the importance of parental relationships and peer behavior on adolescent substance use. Limitations and future directions are discussed.