OBJECTIVES We compared ablation strategy with antlarrhythmic drug therapy (ADT) in patients with paroxysmal atrial fibrillation (PAF). BACKGROUND Atrial fibrillation (AF) ablation strategy is superior to ADT in patients with an initial history of PAF, but its role in patients with a long history of AF as compared with ADT remains a challenge. METHODS One hundred ninety-eight patients (age, 56 +/- 10 years) with PAF of 6 +/- 5 years' duration (mean AF episodes 3.4/month) who had failed ADT were randomized to AF ablation by circumferential pulmonary vein ablation (CPVA) or to the maximum tolerable doses of another ADT, which included flecainide, sotalol, and amiodarone. Crossover to CPVA was allowed after 3 months of ADT. RESULTS By Kaplan-Meier analysis, 86% of patients in the CPVA group and 22% of those in the ADT group who did not require a second ADT were free from recurrent atrial tachyarrhythmias (AT) (p < 0.001); a repeat ablation was performed in 9% of patients in the CPVA group for recurrent AF (6%) or atrial tachycardia (3%). At 1 year, 93% and 35% of the CPVA and ADT groups, respectively, were AT-free. Ejection fraction, hypertension, and age independently predicted AF recurrences in the ADT group. Circumferential pulmonary vein ablation was associated with fewer cardiovascular hospitalizations (p < 0.01). One transient ischemic attack and 1 pericardial effusion occurred in the CPVA group; side effects of ADT were observed in 23 patients. CONCLUSIONS Circumferential pulmonary vein ablation is more successful than ADT for prevention of PAF with few complications. Atrial fibrillation ablation warrants consideration in selected patients in whom ADT had already failed and maintenance of sinus rhythm is desired.