Postoperative junctional ectopic tachycardia is a potentially life-threatening arrhythmia that is often resistant to conventional antiarrhythmic drugs. Amiodarone was suggested to be an adequate treatment; however, data regarding its efficacy and safety are limited. This study evaluated the efficacy of amiodarone in the first-line treatment of postoperative junctional ectopic tachycardia and assessed factors associated with failure of amiodarone therapy. The study included 40 pediatric cardiosurgical patients with postoperative junctional ectopic tachycardia. Intravenous amiodarone in 2-mg/kg boluses and, if necessary, as continuous infusion (10 to 15 mug/kg/min), were used as the first-line therapy. Restoration of sinus rhythm or slowing of junctional ectopic tachycardia to a rate that allowed atrial or atrioventricular sequential pacing was considered as efficacy of therapy. Amiodarone was effective in 18 patients (45%). Sinus rhythm was achieved in 7, and heart rate decreased in 11 patients from 180 (range, 173 to 200) to 142 (range, 133-155) beats/min (p < 0.0001) and allowed effective pacing with atrioventricular synchrony. Higher arteriovenous oxygen saturation difference (p = 0.007) and lower body temperature (p = 0.02) were associated with failure of amiodarone therapy. Amiodarone as the first-line treatment was effective in almost half of the patients with postoperative junctional ectopic tachycardia. Higher arteriovenous oxygen saturation difference and lower body temperature were associated with failure of amiodarone therapy, and their presence may suggest more aggressive initial approach consisting of amiodarone combined with hypothermia.