OBJECTIVE Abnormal plasma concentrations of von Willebrand factor (vWF), a marker of prothrombotic risk, have been found in atrial fibrillation (AF) patients, but the extent of this variation is not clear. This study aimed to investigate the effect of different clinical forms of AF on plasma concentrations of vWF at different levels of the circulatory tree, both intracardiac and extracardiac. RESULTS Peripheral (Pf), left atrial (LA), and coronary sinus (CS) blood samples were obtained during cardiac catheterization from 52 patients with paroxysmal AF (PAF), 36 with persistent AF (PsAF), and 17 control subjects (Ct) with left-sided accessory pathway Wolff-Parkinson-White syndrome. Plasma concentrations of vWF were determined by immunoturbidimetry. Compared with Ct, patients with PAF had higher LA plasma levels of vWF (P = 0.004), but similar Pf and CS levels (both P > 0.30). In contrast, patients with PsAF had higher plasma concentrations of vWF in Pf (P = 0.04), LA (P < 0.001), and CS (P = 0.04) samples compared with Ct. Left atrial plasma concentrations of vWF in patients with PsAF were also higher than in the PAF group (P = 0.04). CONCLUSIONS Regardless of the clinical form of the arrhythmia, AF patients presented significantly higher plasma concentrations of vWF compared with sinus rhythm controls. Multilevel vWF plasma concentration assessment suggests an association between the clinical evolution of AF and the progression of endothelial dysfunction. Further studies will have to establish the exact mechanisms that link endothelial dysfunction and stroke in the context of AF.