Antiphospholipid antibodies (APAs) have been reported in various clinical conditions. However, the pathogenesis and clinical significance of these antibodies are still unclear. The objective of this study was to assess the prevalence of APAs in patients with chronic alcohol- or hepatitis C virus (HCV)-related liver disease and to evaluate their relation to the underlying liver disease. We prospectively studied 201 patients referred to an hepato-gastroenterology department, including 77 patients with a history of alcohol abuse (group I) and 124 with chronic HCV infection (group II), and 107 healthy subjects (control population). Liver biopsy was performed in all patients. In cirrhotic patients, the severity of the liver disease was assessed with the use of Child's classification, as modified by Pugh. Several biologic parameters, including lupus anticoagulant and anticardiolipin antibodies, were determined. Forty-eight percent of patients in group I and 33% of those in group II had APAs. Among cirrhotic patients, APAs were more frequent in patients with Child grade B or C than in those with grade A severity. In patients with chronic HCV-related liver disease, a correlation was found between APA levels and liver fibrosis (P = 0.009); no relation was found between APA levels and histologic liver disease activity (P = 0.25). In the control group, one subject was APA-positive. None had lupus anticoagulant. APAs seem to be frequently associated with chronic liver disease of various causes. These results suggest further investigations on the potential role of these antibodies in fibrosis or liver injury.