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Background: The presence of epicardial connections (ECs) between pulmonary veins (PVs) and other anatomic structures may hinder PV isolation. In this study, we analyzed their prevalence, location, associated factors, and clinical implications. Methods: Five hundred thirty-four consecutive patients with atrial fibrillation undergoing radiofrequency ablation were included. We considered that an EC was present if: (1) the first pass around the PV antrum did not produce PV isolation and (2) subsequent atrial activation during PV pacing showed that the earliest site was located away from the ablation line and later activation sites were observed near the ablation line. Clinical and electrophysiological variables were collected from all patients. Patients were followed during 12.9±9.4 months, and any documented atrial tachyarrhythmia after the 3-month blanking period was classified as a recurrence. Results: Out of the 534 patients included, 72 (13.5%) were found to have 81 ECs. There was a significant association between the presence of ECs and structural heart disease (15.3% in patients without ECs versus 36.5% in patient with ECs; P P =0.002). The presence of a left common trunk was significantly associated with the absence of ECs (29.6% in patients without ECs versus 16.2% in patients with ECs; P =0.014). Patients with ECs had lower acute success in PV isolation compared with patients without ECs (99.1% versus 86.1%; P P =0.04). Conclusions: ECs between PVs and other adjacent structures are frequent in patient with atrial fibrillation (prevalence: 13.5%). Structural heart disease and a patent foramen ovale are strongly associated with the presence of ECs. ECs reduce the acute and chronic success of PV isolation.