Numerous prospective studies have shown that children diagnosed with attention deficit/hyperactivity disorder (ADHD) are at higher risk of long-term substance abuse/dependence. However, there are three important limits to these studies: (a) most did not differentiate the role of hyperactivity and inattention; (b) most did not control for associated behavioral problems; and (c) most did not consider females. Our aim was to clarify the unique and interactive contributions of childhood inattention and hyperactivity symptoms to early adulthood substance abuse/dependence. Behavioral problems of 1803 participants (814 males) in a population-based longitudinal study were assessed yearly between 6 and 12 years by mothers and teachers. The prevalence of substance abuse/dependence at age 21 years was 30.7% for nicotine, 13.4% for alcohol, 9.1% for cannabis and 2.0% for cocaine. The significant predictors of nicotine dependence were inattention (odds ratio (OR): 2.25; 95% confidence interval (CI): 1.63-3.11) and opposition (OR: 1.65; 95%: 1.20-2.28). Only opposition contributed to the prediction of cannabis dependence (OR: 2.33; 95% CI: 1.40-3.87) and cocaine dependence (OR: 2.97; 95% CI: 1.06-8.57). The best behavioral predictor of alcohol abuse/dependence (opposition) was only marginally significant (OR: 1.38; 95% CI: 0.98-1.95). Frequent oppositional behaviors during elementary school were clearly the most pervasive predictors of substance abuse/dependence in early adulthood. The association of childhood ADHD with substance abuse/dependence is largely attributable to its association with opposition problems during childhood. However, inattention remained an important predictor of nicotine dependence, in line with genetic and molecular commonalities between the two phenotypes suggested in the literature.