Aims A new strategy for anatomically based ganglionated plexi (GP) ablation for the treatment of paroxysmal atrial fibrillation (AF) has been proposed recently. We aimed to assess the long-term outcome of patients undergoing anatomic GP ablation for paroxysmal AF, in comparison with circumferential pulmonary vein (PV) isolation. Methods and results The study population consisted of 70 patients (mean age 56.6 +/- 10.9 years; 41 males) with paroxysmal AF and no history of structural heart disease: 35 subjects underwent anatomic GP ablation, while 35 consecutive patients had circumferential PV isolation (CPVI) (control group). The groups were not different in demographic and clinical parameters. Anatomic GP ablation required more ablation points (85.6 +/- 5.5 vs. 74.4 +/- 6.2, P < 0.05) and equal duration of total procedure and fluoroscopy times. During a mean follow-up period of 36.3 +/- 2.3 months, freedom from any atrial tachyarrhythmia without antiarrhythmics was achieved in 34.3% patients after anatomic GP ablation and 65.7% patients after CPVI (log-rank test P = 0.008). Early arrhythmia recurrences and anatomic GP ablation were independent predictors of late recurrence [HR 6.44 (CI 95%; 3.14-13.18; P < 0.001) and HR 2.08 (CI 95%; 1.03-4.22; P = 0.04), respectively]. Six patients in the group of GP ablation underwent subsequent CPVI, plus peri-mitral flutter ablation in two of them, with no further arrhythmia episodes in five patients. Conclusion Anatomic GP ablation yields a significantly lower success rate over the long-term follow-up period, when compared with CPVI. Recurrences include AF and macro re-entrant atrial tachycardias.