Background: A tailored approach targeting complex fractionated electrograms (CFE) has been proposed in catheter ablation of atrial fibrillation (AF). Comparison of clinical outcomes between pulmonary vein (PV) isolation only versus additional CFE ablation (electrogram-guided ablation, EGA) in patients with paroxysmal AF (PAF) has not been reported. Objective: We hypothesized that CFE ablation in addition to the anatomical PV isolation would have an additive effect in long-term maintenance of sinus rhythm in patients with paroxysmal AF. Methods: The study involved 62 patients with symptomatic, drug-refractory paroxysmal AF which remained inducible after PVI. Patients were non-randomly assigned to control group (PVI alone, group I, n=31) or EGA group (PVI with additional CFE ablation, group II, n=31). Results: 1. EGA rendered AF non-inducible in 12/31 patients (38.7%), and converted inducible AF into inducible atrial flutters in 12/31 patients (38.7%). AF remained inducible in 7 patients (22.6%) after the combined ablation procedures. 2. After a mean follow-up of 18.3 months, 9 patients experienced symptomatic recurrence of AF in group I, while AFL was the major mechanism of recurrent arrhythmias in group II patients (AFL in 5/6 and AF in 1/6 patient). 3. Number of patients dependent on antiarrhythmic medication due to recurrent symptomatic atrial tachyarrhythmias was significantly higher (7 vs. 1) in group I than in group II patients. Conclusion: EGA targeting CFE following PVI significantly reduced AF recurrence, and dependence on antiarrhythmic medication compared with PVI alone in patients with PAF.