INTRODUCTION: Heterogeneities in electrophysiological properties may contribute to the development of atrial fibrillation, and regional disparities in endocardial voltage in the left atrium have been related to arrhythmogenic mechanisms. This study aimed at investigating endocardial voltage in different regions of the left atrium in patients with atrial fibrillation (AF). METHODS AND RESULTS: Thirty-six patients (aged 56 +/- 7 years, 10 female) scheduled for circumferential ablation for paroxysmal AF were studied. Voltage measurements were performed during AF and with constant right ventricular pacing in the anterior, posterior, superior and inferior walls outside the antrum of the left (LPV), and right (RPV) pulmonary veins, by means of electroanatomical mapping. There was a high agreement among measurements performed in the endocardium of the posterior atrial wall (ICC > 0.70), and moderate agreement among measurements performed in the superior and inferior walls (0.50 < ICC< 0.70), outside both PV antra. The posterior left atrial wall demonstrated significantly higher voltages both outside the LPV antrum (1.29 +/- 1.36 mV) and the RPV antrum (1.20 +/- 0.63 mV) compared to the inferior, anterior and superior walls (0.47 +/- 0.49, 0.68 +/- 0.69, and 0.61 +/- 0.83 mV outside the LPV antrum, and 0.39 +/- 0.23, 0.65 +/- 0.49, and 0.49 +/- 0.24 mV outside the RPV antrum, respectively). Fractionated electrograms were mainly identified at the posterior left atrial wall, outside the right PV antrum. CONCLUSION: During AF, the posterior wall displays significantly higher voltage and electrogram fractionation compared with other parts of the left atrial endocardium outside the antra of both pulmonary veins in patients with paroxysmal AF.