Beat-to-beat variation in blood flow dynamics during atrial fibrillation (AF) has been associated with evidence of endothelial dysfunction. The aim of the present work is to confirm endothelial dysfunction in patients with AF and test the hypothesis that endothelial dysfunction is reversible upon restoration of normal sinus rhythm. Endothelium-dependent (flow-mediated dilation [FMD]) and endothelium-independent (nitroglycerin-mediated dilation [NMD]) vasodilator function of the brachial artery were measured using high-resolution ultrasound in 46 patients with persistent AF who were scheduled for internal electrical cardioversion and in 25 control subjects. In patients who remained in sinus rhythm after cardioversion, these measurements were repeated after 24 hours (n = 32) and 1 month (n = 19). Compared with control subjects, patients (n = 32) showed lower FMD during AF (8.1 +/- 3.6% vs 12.2 +/- 3.2%, respectively, p <0.001) and similar NMD (17.0 +/- 3.5% vs 15.9 +/- 3.1%, respectively, p = 0.21). In 19 patients who remained in sinus rhythm, FMD increased at both 24 hours (8.0 +/- 3.9% vs 10.6 +/- 4.6%, p = 0.015) and 1 month (8.0 +/- 3.9% vs 13.6 +/- 5.3%, p <0.001). In contrast, NMD was not significantly altered at 24 hours or 1 month after sinus rhythm restoration (17.1 +/- 3.9% vs 17.2 +/- 4.0% vs 16.9 +/- 4.1%). In conclusion, AF is associated with impairment in endothelial function that improves after sinus rhythm restoration.