OBJECTIVE The pathogenetic mechanisms of development of non-alcoholic steatohepatitis (NASH) and fibrosis are not clear, although thrombosis of small intrahepatic veins has been suggested to trigger liver tissue remodelling and thrombotic risk factors have been associated with more advanced fibrosis in chronic viral hepatitis (CVH). We evaluated the prevalence of thrombotic risk factors (RFs) in non-alcoholic fatty liver disease (NAFLD) and their possible association with fatty liver or NASH. METHODS We included 60 patients with histologically documented NAFLD and a historical cohort of 90 patients with chronic hepatitis B (n=39) or C (n=51). Thrombophilic factors were evaluated on the day of the liver biopsy. RESULTS One or more thrombotic RFs were detected in 37% of NAFLD patients, and >or= 2 RFs were detected in 12% of NAFLD patients, being less frequently present than in CVH patients (37% and 68%, respectively; P <or= 0.001). Among NAFLD cases, one or more thrombotic RFs were significantly more frequently present in NASH than simple fatty liver (56% vs. 8%; odds ratio [OR]: 13.8, 2.8-67.4, P<0.001). In multivariate analysis, NASH was independently associated with moderate to severe steatosis (adjusted OR: 24.3; P=0.001) and the presence of one or more thrombotic RFs (adjusted OR: 38.7; P=0.002). Fibrosis stage was worse in NASH patients with than without thrombotic RFs (2.5+/-1.1 vs. 1.3+/-1.1; P=0.002). CONCLUSIONS Thrombotic RFs are frequently present in patients with NAFLD and are associated with NASH and more advanced fibrosis. Such an association may have significant clinical implications, even though it is not clear yet whether it represents a primary or secondary phenomenon.