BACKGROUND Atrial fibrillation (AF) may recur after pulmonary vein isolation (PVI) as the result of either recurrent PV conduction or non-PV foci. This study characterized the electrophysiological findings of patients with recurrent AF after initially successful PVI and the clinical outcome after a repeat procedure. RESULTS Among 185 patients undergoing PVI, 52 reported no significant improvement in their clinical course. We analyzed PV conduction in 51 PVs (15 patients) at repeat PVI. All PVs were isolated with either RF (30 W, 50 degrees C, 60 seconds) or cryoablation (-80 degrees C for 5 minutes). At repeat study, 42 of the previously isolated 51 PVs had return of conduction. All patients had recurrent conduction in > or =2 PVs, with only 1 non-PV focus identified. The mean number of RF applications required to re-isolate the PVs was fewer at the repeat compared with the initial procedure (10+/-6 versus 4+/-2, P<0.005). Over a period of 15+/-6 months, all but 1 patient was clinically improved by the second procedure. CONCLUSIONS In patients with recurrent AF after PVI, return of PV conduction can be expected. Repeat PVI provides significant clinical benefit for these patients. These results suggest that if permanent PV isolation is the ablation strategy, different techniques may be required to improve long-term efficacy.