INTRODUCTION: There are very few data assessing a family history of venous thromboembolism (VTE) as a risk factor for VTE. This question is nonetheless of interest as inherited risk factors are involved but at least partly unknown. METHODS: The E.D.I.TH. study is a prospective hospital-based case-control study. The family history was assessed by using a standard questionnaire, considering the total number of the first-degree relatives and the number of these relatives who had suffered from VTE. We analysed 698 first VTE cases and their matched controls, 507 pairs without and 191 pairs with a major acquired risk factor (active malignancy, surgery or plaster cast in the past three months, pregnancy or delivery in the past three months). RESULTS: A family history of VTE was associated with VTE occurrence, irrespective of carrying or not factor V Leiden mutation or G20210A prothrombin gene mutation and irrespective of the presence or absence of major acquired risk factors; adjusted conditional odds ratio: 2.7 (95%CI, 1.8-3.8). CONCLUSION: A family history might well be considered when estimating type and duration of prophylaxis for VTE specifically in patients with active cancer or who experienced surgery. Family history of VTE could be added to a prior VTE history to define a concept of clinical thrombophilia which is not necessarily related to carrying a known inherited risk factor.