This study evaluated the interplay of attention deficit hyperactivity disorder (ADHD) symptom severity, deviant peer group affiliation, oppositional defiant disorder (ODD), and conduct disorder (CD) as risk factors among 142 adolescents with childhood ADHD. Deviant peer affiliation mediated the relation between childhood ADHD symptoms and 6 substance use and abuse variables. Moreover, moderated mediation analyses found that for children with high levels of ODD and CD symptoms, the mediated effect of ADHD through deviant peer affiliation was significant; however, for children with low levels of ODD and CD symptoms, this mediated effect was weak and nonsignificant. Results suggest that children with severe ADHD symptomatology and comorbid antisocial behavior are at highest risk for peer-mediated substance use in adolescence.