Esmolol is often used in the acute management of children with arrhythmias and/or hypertension; however, pharmacokinetic studies of the drug in children have been limited. The objective of this study was to determine the pharmacokinetics of esmolol in children with a history of supraventricular arrhythmias (SVT) who were scheduled for diagnostic electrophysiology study or a catheter ablation procedure. Subjects were stratified into two age groups: 2–11 and 12–16 years. After an episode of stimulated or spontaneous SVT, esmolol was administered intravenously as a 1,000 μg/kg bolus followed by continuous infusion at 300 μg/kg/min. Blood samples were collected before, at 5, 10 and 15 min after the loading dose, and 3, 6, 9, 12, 15 and 20 min after the end of the infusion. Plasma concentration of esmolol was quantitated by a specific LC/MS assay. Pharmacokinetic data were available for 25 subjects. Arterial esmolol concentrations were approximately five times greater than venous concentrations. Esmolol had an extremely short distribution half-life (0.6 min), a rapid terminal elimination half-life (6.9 min), and a rapid clearance (119 ± 51 mL/min/kg) which was not related to subject age or weight. Seventeen of the subjects (63%) converted to normal sinus rhythm in an average of 2 min (range 0–5 min). The pharmacokinetics of esmolol and its efficacy in terminating SVT in children is similar to that observed in adults.