Pulmonary vein (PV) disconnection by radiofrequency (RF) catheter ablation has been reported to cure atrial fibrillation (AF). Different techniques have been proposed. The aim of this study was to evaluate the technical limitations of both anatomical and electrophysiological approaches. A total of 110 PVs were ablated in 26 consecutive patients (23 male, 3 female, mean age 51 +/- 9.5 years) with paroxysmal (n = 19, 73%), persistent (n = 3, 12%) or permanent (n = 4, 15%) AF. Accurate reconstructions of the PV ostia were obtained using fluoroscopy, electrophysiology, and the CARTO mapping system. Electrophysiological mapping was attempted in all PVs by means of a decapolar circular catheter. RF ablation was performed in a single-blind fashion in order to anatomically create circumferential lines around each PV. Completeness of anatomically-guided, circumferential RF lesions around the PVs was established by the physician using the CARTO system, who was unaware of the decapolar circular catheter electrophysiological recordings of the PVs. If PV potentials persisted, RF delivery was targeted to the electrophysiological breakthroughs. All PV ostia were anatomically ablated by performing circumferential RF lesions. Among 110 PVs, 73 (66%) were fully mapped by use of circular catheters. After anatomical ablation, electrical disconnection was achieved in 44/73 PVs (60%). In the remaining 29 PVs (40%), a median of one RF pulse (mean 1.8 +/- 1.4) was necessary to achieve complete PV disconnection. Total procedure duration, fluoroscopy time, and RF delivery time were 232 +/- 29, 50 +/- 16 and 39 +/- 11 min, respectively. Pericardial effusion occurred in one patient after the procedure. After 10.5 +/- 6.4 months, 21 patients (81%) were in stable sinus rhythm and 13 of them (62%) discontinued all drugs after 6 months. Only 4 patients (15%) required two procedures. Electrical PV disconnection cannot be achieved in many PVs by means of a pure anatomical approach. On the other hand, electrophysiological mapping cannot be performed in many PVs owing to anatomical variations. An integrated approach might overcome these limitations.