We report a double-blind, multicenter, multinational, placebo-controlled, and well-controlled trial to prove that the sustained-release (SR) formulation of propafenone is superior to placebo in preventing symptoms of paroxysmal atrial fibrillation (AF). A total of 594 patients were enrolled in the qualifying period of the study and 293 patients were randomized at 53 centers. There were significant increases in the arrhythmia-free periods from day 5 of randomization to the first recurrence of symptomatic atrial arrhythmia in the propafenone SR 325 mg twice daily (p = 0.004) and propafenone SR 425 mg twice daily (p = 0.003) treatment groups compared with placebo. The median arrhythmia-free time was 9 days in the placebo group, 35 days in the propafenone SR 325 mg twice daily group, and 44 days in the propafenone SR 425 mg twice daily group. There was a significant reduction in average heart rate during the first recurrence of symptomatic arrhythmia after day 5 in the low-dose propafenone group compared with placebo. The median treatment failure time from day 5 (arrhythmia recurrence, adverse events, and withdrawals) was prolonged from 8 days in the placebo group to 19 days in the propafenone SR 325 mg twice daily group (p = 0.002) and to 24 days in the propafenone SR 425 mg twice daily group (p = 0.006). The percentage of patients with ≥1 serious adverse event was similar in the propafenone SR treatment groups (propafenone SR 325 mg twice daily, 10.0%; propafenone SR 425 mg twice daily, 11.2%) but lower in the placebo group (1.1%). In conclusion, the SR formulation of propafenone is superior to placebo, well-tolerated, and prevents symptoms of paroxysmal AF.