The purpose of this study was to clarify the change in the quality of life (QOL) and clinical outcomes following segmental pulmonary vein (PV) isolation for paroxysmal atrial fibrillation (AF) in 50 patients with drug-refractory, paroxysmal AF. The left superior, left inferior, and right superior PVs were targeted for isolation in all patients, and the right inferior PV was isolated in 4 patients. AF recurred in 22 of 50 patients, and these patients were treated with class I or class III antiarrhythmic drugs that had been ineffective before the ablation procedure. The symptom severity and frequency was scored and the QOL was assessed using the Short-Form-36 questionnaire (SF-36) before the PV isolation and at the end of the follow-up period (6.0+/-3.0 months). PV isolation resulted in a reduction in the symptom severity (p<0.001) and symptom frequency (p<0.001) scores as compared with the pre-ablation values. Ninety percent of the patients had a >90% reduction in the frequency of symptomatic episodes of AF after the ablation procedure. The mean SF-36 physical and mental component summary scores also significantly improved after PV isolation as compared with the pre-ablation values (both for p<0.001). With a segmental isolation approach that targets at least 3 PVs, satisfactory improvement in the symptoms and QOL can be achieved in patients with drug-refractory, paroxysmal AF.