To describe the national scope and magnitude of outpatient adverse drug events (ADEs) that lead to emergency department (ED) visits in children and adolescents. To conduct an active surveillance of patients 18 years of age or younger who came to EDs with ADEs from Jan 1, 2004, to Dec 31, 2005, through a nationally representative, stratified probability sample of 63 US hospitals with EDs. The main outcome measures were national estimates of the number, type, patient demographics, and clinical characteristics of ADEs. Annually, an estimated 158,520 patients </=18 years old (95% CI, 117,745-199,295; 2 per 1000 persons) were treated in EDs for ADEs. Almost half (49.4%) of these visits occurred in patients between 1 and 4 years of age. Unintentional overdoses were the most common type of ADE (44.9%), followed by allergic reactions (35%), and adverse effects (12.6%). Antimicrobial agents, analgesic medications, and respiratory medications accounted for almost half of ADEs (25.2%, 13.7%, and 10.6%, respectively). Fewer than 1 in 10 patients (9.5%) required hospitalization or extended observation. Interventions targeting unintentional overdoses of medications commonly given to preschool-aged children would likely have the highest impact in reducing ED visits from outpatient ADEs.