BACKGROUND: Despite an initial impressive impact, a critical appraisal of the link between pregnancy loss and inherited thrombophilias is currently growing. Furthermore, little is known about the paternal thrombophilic phenotype and pregnancy loss. OBJECTIVE: We sought an association between unexplained pregnancy loss and parental factor V Leiden (FVL) and Prothrombin G20210A (PTG) mutations. METHODS: Design - Incident case-control study. Setting- University Hospital of Brest (France). Patients - Women and their partners from the West Brittany area, consecutively referred for unexplained pregnancy losses (two or more consecutive losses at or before 21 weeks of gestation, or at least one later loss). Controls - Women and their partners with no history of pregnancy loss and at least one normal pregnancy, from the same geographic area, recruited using electoral lists. Statistical analysis - Comparison of FVL and PTG allele frequency between cases and controls using the chi-square test. Separate analyses were performed according to the type of pregnancy loss (early recurrent or later loss). RESULTS: 311 women (mean age: 32.8) and 284 of their partners were enrolled as cases while 599 women (mean age: 34.3) and 297 of their partners were recruited as controls. The prevalence of female, male or couple thrombophilic mutations was not statistically different between cases and controls whatever the definition of pregnancy loss retained. CONCLUSIONS: Presently, there is no clinical indication to routinely test for FVL and likely PTG mutations in women with early recurrent pregnancy loss. Moreover, our results did not reveal that paternal thrombophilic polymorphism should be further explored.