This study was designed to assess adverse effects of oral propafenone in a large number of pediatric patients. Retrospective data from 27 European centers covering 772 patients treated with oral propafenone were analyzed. The following arrhythmias were treated: reentrant supraventricular tachycardia in 388 patients, atrial ectopic tachycardia in 66, junctional ectopic tachycardia in 39, atrial flutter in 21, ventricular premature complexes in 140, ventricular tachycardia in 78, and other arrhythmias in 39 patients. Two hundred forty-nine patients (32.3%) had structural heart disease. Significant electrophysiologic side effects and proarrhythmia were found in 15 of 772 patients (1.9%): sinus node dysfunction in 4, complete atrioventricular block in 2, aggravation of supraventricular tachycardia in 2, acceleration of ventricular rate during atrial flutter in 1, ventricular proarrhythmia in 5, and unexplained syncope in 1 patient. Cardiac arrest or sudden death occurred in 5 of 772 patients (0.6%): 2 patients had supraventricular tachycardia due to the Wolff-Parkinson-White syndrome and a normal heart; the remaining 3 patients had structural heart disease. Overall, adverse cardiac events were more common in the presence (12 of 249 patients, 4.8%) than in the absence (8 of 523 patients, 1.5%) of structural heart disease (p <0.01). There was no difference between patients treated for supraventricular and ventricular arrhythmias. Thus, propafenone is a relatively safe drug for the treatment of several pediatric tachyarrhythmias. Proarrhythmic effects seem to be less frequent than those reported for encainide or flecainide and occur predominantly in patients with structural heart disease.