This study examined psychosocial correlates of prescription drug misuse over time among young adults. Data from a nationally representative U.S. sample consisting of 4882 cases were analyzed. Multivariate logistic regression analyses revealed that being younger, having less education, as well as alcohol use; marijuana use, inhalant use, and delinquent behavior during adolescence were associated with prescription drug misuse. In Whites, prescription drug misuse was related to age, alcohol use, marijuana use and delinquent behavior. Among Hispanic young adults inhalant use, delinquent behavior and maternal warmth were associated with greater prescription drug use, while marijuana use was predictive of lower prescription drug misuse. Religious attendance was associated with lower prescription drug misuse among Black young adults. These findings suggest that there are unique racial/ethnic profiles for substance use risk behaviors in adolescence. Further investigations should examine culturally specific dimensions culturally specific dimensions that may account for racial/ethnic differences in prescription drug misuse.