Background: Adolescents with attention-deficit/hyperactivity disorder (ADHD) are known to be at significantly greater risk for the development of substance use disorders (SUD) compared to peers. Impulsivity, which could lead to higher levels of drug use, is a known symptom of ADHD and likely accounts, in part, for this relationship. Other factors, such as a biologically increased susceptibility to substance dependence (addiction), may also play a role. Objective: This report further examines the relationships between childhood ADHD, adolescent- onset SUD, and substance abuse and substance dependence in adulthood. Method Individuals with childhood ADHD and non-ADHD controls from the same population-based birth cohort were invited to participate in a prospective outcome study. Participants completed a structured neuropsychiatric interview with modules for SUD and a psychosocial questionnaire. Information on adolescent SUD was obtained retrospectively, in a previous study, from medical and school records. Associations were summarized using odds ratios (OR) and 95% CIs estimated from logistic regression models adjusted for age and gender. Results: A total of 232 ADHD cases and 335 non-ADHD controls participated (mean age, 27.0 and 28.6 years, respectively). ADHD cases were more likely than controls to have a SUD diagnosed in adolescence and were more likely to have alcohol (adjusted OR 14.38, 95% CI 1.49–138.88) and drug (adjusted OR 3.48, 95% CI 1.38–8.79) dependence in adulthood. The subgroup of participating ADHD cases who did not have SUD during adolescence were no more likely than controls to develop new onset alcohol dependence as adults, although they were significantly more likely to develop new onset drug dependence. Conclusions: Our study found preliminary evidence that adults with childhood ADHD are more susceptible than peers to developing drug dependence, a disorder associated with neurological changes in the brain. The relationship between ADHD and alcohol dependence appears to be more complex