OBJECTIVE This study compared the safety and efficacy of digoxin and flecainide in the prophylaxis of supraventricular tachycardia in infants. BACKGROUND Recurrence of supraventricular tachycardia in infants is common. Digoxin is the conventional drug of first choice for prophylaxis, but its efficacy has not been tested in a controlled clinical trial, and there is no consensus on the drug of choice when digoxin is ineffective. METHODS We reviewed retrospectively the records of all infants with supraventricular tachycardia due to atrioventricular (AV) reentry admitted to our hospital between January 1986 and December 1993. RESULTS Thirty-nine infants presented with sustained AV reentrant tachycardia at age 1 to 330 days (median 12). Intravenous flecainide was required to maintain immediate control in six patients who were then treated with oral flecainide. The other 33 patients were treated with oral digoxin. There was no recurrence of tachycardia in 14 (42%) of the 33 patients (95% confidence interval [CI] 25% to 61%). In the other 19 patients (58%) (95% CI 39% to 75%), digoxin was replaced by oral flecainide because of multiple recurrence of tachycardia. Full control was achieved in all 19 of these patients (100%) (95% CI 82% to 100%) and in 5 of the 6 patients treated with both intravenous and oral flecainide. Thus, overall, flecainide was effective in 24 (96%) of 25 patients (95% CI 80% to 100%). CONCLUSIONS Comparison with previous natural history studies suggests that digoxin is ineffective in the prophylaxis of supraventricular tachycardia. Oral flecainide was effective in a small number of infants, with no adverse effects (95% CI 0% to 12%), and may now be preferred as the primary prophylactic agent.