Objective: To compare the safety and efficacy of atomoxetine, a selective inhibitor of the norepinephrine transporter, versus placebo in Attention-Deficit/Hyperactivity Disorder (ADHD) patients with comorbid Oppositional Defiant Disorder (ODD). Methods: A subset analysis of 98 children from two identical, multi-site, double-blind, randomized, placebo-controlled trials involving 9 weeks of treatment with atomoxetine or placebo was conducted. Patients met DSM-IV ADHD criteria. ODD was diagnosed with the Diagnostic Interview for Children and Adolescents-IV (DICA-IV; Reich, Welner, & Herjanic, 1997). ADHD severity was assessed with the ADHD Rating Scale-IV-Parent Version: Investigator Administered and Scored (ADHD-RS-IV-Parent:Inv; DuPaul, Power, Anastopoulos, & Reid, 1998); the short version of the Conners' Parent Rating Scales-Revised (CPRS-R:S; Conners, 2000); and the Clinical Global Impressions of ADHD Severity (CGI-ADHD-S; Guy, 1976). Clinical response was defined as a greater than or equal to 25% reduction in ADHD-RS-IV-Parent:Inv total score. Results: ADHD-RS-IV-Parent:Inv, CGI-ADHD-S, and three CPRS-R:S subscale scores improved markedly with atomoxetine treatment. However, a decrease in the CPRS-R:S Oppositional subscore for atomoxetine-treated patients was not significantly greater than scores for placebo-treated patients. Clinical response rates were 65.4% in the atomoxetine group, and 36.4% in the placebo group (p = 0.007). Conclusion: Atomoxetine was effective for the treatment of ADHD in patients with comorbid ODD. It did not significantly reduce the severity of ODD symptoms, and was well tolerated by the patients. (Contains 2 figures and 5 tables.)