Background: Isolation of arrhythmogenic pulmonary veins (PVs) by radiofrequency current (RF) application has been introduced as a curative treatment for patients (pts) with paroxysmal atrial fibrillation (AF). The present study sought to investigate the feasibility and efficacy of this approach guided by conventional and electroanatomical mapping (CARTO®). Methods: Twenty pts (13 male; 57 ± 8 years) with recurrent documented focally triggered idiopathic AF refractory to multiple antiarrhythmic drugs were prospectively included. Atrial premature beats were present at baseline in 9 pts and could be provoked in further 8 pts. Empirical ablation of both superior PVs was performed in 3 pts with no focal activity. After transseptal puncture selective angiography of all PVs was obtained. Thirty-six PVs (left superior: n = 18, right superior: n = 10, left inferior: n = 8) were targeted for RF ablation. A complete left atrial CARTO®—map including the left atrial (LA) to pulmonary vein (PV) junction was obtained during sinus rhythm and/or coronary sinus pacing. RF was initially applied at the PV-LA junction at areas with the shortest left atrial- to PV potential interval (target 50°C, max. 30 W, duration 60 sec). Isolation was confirmed by the complete disappearance of specific PV potentials. RF lesions were analyzed with respect to the number of segment-quarters covering the PV ostium. Results: Functional isolation could be achieved in 35 out of 36 PVs following 10 ± 5 RF applications for each PV. RF applications covered 2 or less quarter segments of the overall PV circumference in 29 (80%) PVs. Total session duration was 6.5 ± 1.6 h with a mean fluoro-time of 54 ± 18 minutes. For CARTO® mapping and ablation a mean fluoro time of 34 ± 6 min was required. During a mean follow up period of 8.3 ± 2.5 months AF relapsed in 9 pts (46%). A second approach was performed in 5 pts. and demonstrated either new foci (n = 2) or recurrence of previously isolated PV (n = 8). The second RF ablation procedure led to stable sinus rhythm in 3 out 5 pts. Thus, the overall successrate including the second procedure was 70%. Conclusions: CARTO® guided functional isolation of presumed arrhythmogenic PVs by RF lesions covering 2 or less segments of the PV ostium in most patients is feasible. However, repeat procedures are often warranted to permanently treat paroxysmal atrial fibrillation.