OBJECTIVES: To evaluate the use of ondansetron in a tertiary care pediatric health system, assess the incidence of ventricular tachyarrhythmia within 24 hours of ondansetron, and identify the characteristics of children experiencing a ventricular tachyarrhythmia after ondansetron, to identify potential risk factors. STUDY DESIGN: This retrospective chart review identified children =18 years of age who received ondansetron within 24 hours prior to a ventricular tachyarrhythmia. Those identified were evaluated for other diagnoses, concomitant medication use, electrolyte abnormalities, or underlying conduction abnormalities that may have contributed to the arrhythmia. RESULTS: A total of 199 773 doses of ondansetron were administered to 37 794 patients over 58 009 visits. Average dose was 0.13 mg/kg/dose (range 0.005-0.86 mg/kg/dose). Seven patients received ondansetron within 24 hours prior to a ventricular arrhythmia. All 7 patients had underlying congenital cardiac conduction abnormalities (n = 3) or other major cardiac diagnoses (n = 4). In clinical review, torsades de pointes was found in only 1 of the 7 patients. CONCLUSIONS: This retrospective study found the risk of ventricular arrhythmia within 24 hours after ondansetron administration was 3 in 100 000 patients treated annually (0.003%). Children with major cardiac conditions could be considered for electrocardiogram screening and continuous cardiac monitoring while receiving ondansetron. Our findings do not support recommendations for electrocardiogram screening or continuous monitoring of other pediatric populations receiving ondansetron.