BACKGROUND: Despite their higher rates of stress, African American young adults tend toward similar or lower rates of substance misuse than their White counterparts. Arguably, such patterns derive from: (1) racial variations in the availability of coping strategies that mitigate stress; and/or (2) racial differences in the efficacy of available coping styles for reducing substance misuse. OBJECTIVES: We assessed whether two coping style types-problem-focused and avoidance-oriented-varied by race (non-Hispanic African American vs. non-Hispanic White) and whether the effects of coping styles on substance misuse were moderated by race. METHODS: Using data from a community sample of South Florida young adults, we employed logistic regression analyses to examine racial differences in coping style and to test if race by coping style interactions (race × problem-focused coping and race × avoidance-oriented coping) influenced the odds of qualifying for a DSM-IV substance use disorder, net of lifetime stressful events and sociodemographic controls. RESULTS: We found that African American young adults displayed lower problem-focused coping, and higher avoidance-oriented coping, than did White young adults. Among both African American and White respondents, problem-focused coping was associated with reduced odds of illicit drug use disorder (excluding marijuana), and among Whites, avoidance-oriented coping was associated with increased odds of an aggregate measure of alcohol, marijuana, and other illicit drug use disorders. Among African Americans, however, avoidance-oriented coping was associated with lower odds of marijuana use disorder. CONCLUSION: Substance misuse policies and practices that consider the sociocultural contexts of stress and coping are recommended.