This study explored the relationship between trajectories of affective self-regulation skills during secondary school and young adult substance use in a large multiethnic, urban sample (N = 995). During secondary school, participants completed a measure of cognitive and behavioral skills used to control negative, unpleasant emotions or perceived stress. As young adults, participants reported on the frequency and quantity of their alcohol, cigarette, and marijuana use in a telephone interview. Controlling for demographic variables, self-regulation did not significantly change over adolescence, although there was significant variation in participants' rates of growth and decline. Lower seventh-grade self-regulation and less steep increases in self-regulation were predictive of higher young adult substance use. Male participants had significantly lower initial self-regulation and higher young adult substance use. The results suggest that interventions that build affective self-regulation skills in adolescence may decrease the risk of young adult substance use.