Objective: High rates of substance-use disorders (SUD) have been found in samples of adolescents and adults with attention-deficit/hyperactivity disorder (ADHD). Predictors of SUD in children with ADHD who are at risk for the development of SUDs remain understudied. The main aims of this study were to identify clinically meaningful characteristics of children that predicted the future development of SUDs and to see whether the role of these characteristics varied by sex. Method: Subjects were children and adolescents with (n = 268; mean age plus or minus standard deviation = 10.9 plus or minus 3.2 years) and without (n = 229; mean age 11.9 plus or minus 3.3 years) "DSM-III-R" ADHD followed prospectively and blindly over a 10-year follow-up period onto young adult years. Subjects were assessed with structured diagnostic interviews for psychopathology and SUDs. Results: Over the 10-year follow-up period, ADHD was found to be a significant predictor of any SUD (hazards ratio 1.47; 95% confidence interval 1.07-2.02; p = 0.01) and cigarette smoking (2.38; 1.61-3.53; p less than 0.01). Within ADHD, comorbid conduct disorder (2.74; 1.66-4.52; p less than 0.01) and oppositional defiant disorder (2.21; 1.40-3.51; p less than 0.01) at baseline were also found to be significant predictors of SUDs. Similar results were found for cigarette-, alcohol-, and drug-use disorders. There were few meaningful sex interaction effects. No clinically significant associations were found for any social or family environment factors or for cognitive functioning factors (p greater than 0.05 for all comparisons). Conclusions: These results indicate that ADHD is a significant risk factor for the development of SUDs and cigarette smoking in both sexes. (Contains 2 figures and 2 tables.)