Beyond disease-defining core symptoms of inattention, hyperactivity, and impulsivity, ADHD is characterized by functional impairment of patients. The Columbia Impairment Scale (CIS) is a parent rating scale with relatively strong psychometric properties, tapping four major dimensions: interpersonal relations, psychopathology, schoolwork, and use of leisure time. OBJECTIVES: CIS ratings from the NIMH MTA Study (n=579 children with ADHD according to DSM-IV-criteria) were used as an alternative outcome measure to evaluate the cost-effectiveness of medication management (MedMgt), intense behavioral treatment (Beh), both combined (Comb), or community care (CC) in the study population and in three subgroups: hyperkinetic disorder (according to ICD-10-criteria preferred in Europe); pure HKD or HKD/HKCD, and in pure ADHD, over 14 months. METHODS: For costing (societal and third-party payer's perspectives), patient-level resource utilization data were combined with country-specific unit costs for Germany, Netherlands, Sweden, United Kingdom, and United States (year 2005). Incremental cost-effectiveness ratios (ICERs) were determined using functional improvement (CIS effect size [ES], Cohen's d) as clinical outcome criterion. Four treatment strategies and a hypothetical “Do Nothing” alternative were compared with each other. RESULTS: The four MTA treatment strategies were all clinically effective. Across jurisdictions, both CC versus “Do Nothing” (ICERs ranging from €1,200/ES to €2,600/ES) and MedMgt (ICERs versus “Do Nothing” from €1,000/ES to €2,700/ES, ICERs versus CC from dominance to €3,000/ES) appeared attractive on grounds of cost-effectiveness. MedMgt dominated Beh, and ICERs for Comb versus MedMgt ranged from €500,000/ES to €1,000,000/ES. Results for subgroups with pure ADHD, HKD/HKCD, and pure HKD were broadly similar. Sensitivity analyses including probabilistic evaluations using non-parametric bootstrapping supported these findings. CONCLUSION: Despite notable international differences in terms of diagnostic criteria, standards of care, and unit costs, the cost-effectiveness of MTA-based clinical treatment strategies for patients with pure ADHD seemed remarkably similar across jurisdictions. The impact of comorbidity remains to be explored.