Context Stimulant medication can effectively treat 60% to 70% of youth with attention-deficit/hyperactivity disorder (ADHD). Yet many parents seek alternative therapies, and Hypericum perforatum (St John's wort) is 1 of the top 3 botanicals used.Objective To determine the efficacy and safety of H perforatum for the treatment of ADHD in children.Design, Setting, and Participants Randomized, double-blind, placebo-controlled trial conducted between March 2005 and August 2006 at Bastyr University, Kenmore, Washington, among a volunteer sample of 54 children aged 6 to 17 years who met Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria for ADHD by structured interview.Intervention After a placebo run-in phase of 1 week, participants were randomly assigned to receive 300 mg of H perforatum standardized to 0.3% hypericin (n = 27) or a matched placebo (n = 27) 3 times daily for 8 weeks. Other medications for ADHD were not allowed during the trial.Main Outcome Measures Performance on the ADHD Rating Scale–IV (range, 0-54) and Clinical Global Impression Improvement Scale (range, 0-7), and adverse events.Results One patient in the placebo group withdrew because of an adverse event. No significant difference was found in the change in ADHD Rating Scale–IV scores from baseline to week 8 between the treatment and placebo groups: inattentiveness improved 2.6 points (95% confidence interval [CI], –4.6 to –0.6 points) with H perforatum vs 3.2 points (95% CI, –5.7 to –0.8 points) with placebo (P = .68) and hyperactivity improved 1.8 points (95% CI, –3.7 to 0.1 points) with H perforatum vs 2.0 points (95% CI, –4.1 to 0.1 points) with placebo (P = .89). There was also no significant difference between the 2 groups in the percentage of participants who met criteria for improvement (score ≤2) on the Clinical Global Impression Improvement Scale (H perforatum, 44.4%; 95% CI, 25.5%-64.7% vs placebo, 51.9%; 95% CI, 31.9%-71.3%; P = .59). No difference between groups was found in the number of participants who experienced adverse effects during the study period (H perforatum, 40.7%; 95% CI, 22.4%-61.2% vs placebo, 44.4%; 95% CI, 25.5%-64.7%; P = .78).Conclusion In this study, use of H perforatum for treatment of ADHD over the course of 8 weeks did not improve symptoms.