Children diagnosed with attention-deficit/hyperactivity disorder (ADHD; n = 142) were prospectively monitored into adolescence (13-18 years old) to evaluate their risk for elevated substance use relative to same-aged adolescents without ADHD (n = 100). Probands reported higher levels of alcohol, tobacco, and illicit drug use than did controls. Group differences were apparent for alcohol symptom scores but not for alcohol or marijuana disorder diagnoses. Within probands, severity of childhood inattention symptoms predicted multiple substance use outcomes: childhood oppositional defiant disorder/conduct disorder (ODD/CD) symptoms predicted illicit drug use and CD symptoms. Persistence of ADHD and adolescent CD were each associated with elevated substance use behaviors relative to controls. Further study of the mediating mechanisms that explain risk for early substance use and abuse in children with ADHD is warranted.