OBJECTIVE: To test the hypothesis that propafenone, administered orally, prevents symptomatic paroxysmal supraventricular arrhythmias. DESIGN: a 6-month, open-label, dose-finding phase followed by a randomized, double-blind, placebo-controlled, crossover phase, with each treatment period lasting up to 60 days. SETTING: An outpatient clinic. PATIENTS: Thirty-three patients with either paroxysmal supraventricular tachycardia (n = 16) or paroxysmal atrial fibrillation (n = 17) were enrolled. Their arrhythmias were documented by electrocardiogram before enrollment. Twenty-three patients (14 with paroxysmal supraventricular tachycardia and 9 with paroxysmal atrial fibrillation) were randomized and the data obtained from these patients were used in the efficacy analysis. INTERVENTION: Propafenone (300 mg three times daily in 19 patients, 300 mg twice daily in 3 patients, and 150 mg twice daily in 1 patient) and matching placebo tablets were administered in a randomized sequence. MEASUREMENTS: Symptomatic arrhythmia was documented by telephone transmission of the electrocardiogram. MAIN RESULTS: The time to first recurrence was prolonged for the overall group of 23 patients while they received propafenone (P = 0.004). The recurrence rate of arrhythmia during treatment with propafenone was estimated to be approximately one fifth of the recurrence rate during treatment with placebo. CONCLUSIONS: Propafenone is effective in reducing symptomatic paroxysmal supraventricular arrhythmias.