Objective: To assess how threshold oppositional defiant disorder (ODD), inattention, and hyperactivity-impulsivity affect the response to atomoxetine versus methylphenidate. Method: Systematic review of randomized controlled trials (RCTs; greater than or equal to 6 weeks follow-up). The primary measure was core symptom response--greater than or equal to 40% reduction in ADHD Rating Scale-IV--Parent Version: investigator administered and scored total or domain subscores, as appropriate. Results: Data from 1,391 children and adolescents (823 atomoxetine, 568 methylphenidate; 7 RCTs) were meta-analyzed. The mean difference in response rates for patients with ODD was 0.6% (95% confidence interval [CI] = -11.9%-13.1%). The "without ODD" patient group showed significant between-trial heterogeneity (p less than 0.001). Response rate differences for patients meeting the threshold for inattention or hyperactivity-impulsivity were -3.1% (95% CI = -11.5%-5.3%) and -4.9% (95% CI = -14.3%-4.4%), respectively. Conclusions: Meeting the threshold criteria for oppositionality, inattention, or hyperactivity-impulsivity did not alter core ADHD symptom response to atomoxetine versus methylphenidate, which was equivalent. (Contains 4 tables and 2 figures.)