Among candidate risk factors associated with postoperative venous thromboembolism (VTE), the role of factorV Leiden (FVL) mutation remains unclear. We performed a case-control study to assess the potential significance of FVL mutation in postoperative VTE cases despite prophylaxis. We used data from the ongoing case-control "EDITH" study. We extracted 133VTE cases and 144 controls who had undergone either surgery or had plaster cast in the previous three months. Prophylaxis adequacy with regard to the recommendations published by the American College of Chest Physicians was retrospectively assessed. FVL mutation was present in 20VTE cases and four controls (OR 5.9, 95% CI 2-18). Prophylaxis was judged as adequate in 116 cases (88.5%) and in 129 controls (87.2%) (p=0.66). The frequency of FVL mutation was not different in VTE cases occurring while on adequate prophylaxis and in VTE cases occurring after the end of adequate prophylaxis (p=0.27). FVL mutation was closely associated with postoperative VTE in patients classified as having received an adequate prophylaxis (8.4; 95% CI, 2.4 to 29). This study shows a close association between the presence of factorV Leiden mutation in symptomatic VTE occurring after surgery despite prophylaxis.