Objective: Previous studies comparing atomoxetine and methylphenidate to treat ADHD symptoms have been equivocal. This noninferiority meta-analysis compared core ADHD symptom response between atomoxetine and methylphenidate in children and adolescents. Method: Selection criteria included randomized, controlled design; duration 6 weeks; and assessment of ADHD Rating Scale-IV-Parent Version: Investigator Administered and Scored (ADHDRS) scores. Six-week response rates, defined as [greater than or equal to]40% reduction in ADHDRS total score, were compared using a noninferiority margin of -15%. Results: Seven studies met inclusion criteria (N = 1,368). After 6 weeks, 53.6% (95% confidence interval [CI] 48.6%-58.4%) of atomoxetine-treated patients (n = 811) had responded compared with 54.4% (47.6%-61.1%) for methylphenidate (n = 557), with atomoxetine demonstrating noninferiority to methylphenidate (absolute difference -0.9%, 95% CI -9.2%-7.5%). Conclusion: After 6 weeks of treatment atomoxetine and methylphenidate had comparable efficacy in reducing core ADHD symptoms in children and adolescents. (Contains 2 tables and 4 figures.)