Although considerable research attention is paid to the misuse of controlled medications, a relatively small number of studies focus on prescription opioid misuse (POM) among racial/ethnic minority adolescents. This study aimed to determine the prevalence of POM among adolescents in the three largest racial/ethnic groups (Whites, Hispanics, Blacks) and identify demographic and psychosocial factors that increase the risk of POM. Additionally, the authors applied concepts from social bonding theory and social learning theory to determine the extent to which these concepts explain adolescent POM among each group. Using data from the 2012 National Survey of Drug Use and Health, multivariate logistic regression models were estimated to determine which factors were associated with an increased risk of POM. Results show that Blacks (6.08%) have the highest prevalence rate of adolescent POM and risk factors vary by race/ethnicity. These findings are important in that they enhance the ability of prescribers to identify high-risk adolescent patients and help to make prevention interventions more culturally relevant.