Inherited thrombophilia has been shown to be linked with fetal loss. We performed a case-control study on the association between thrombosis-related polymorphisms in the factor V (FV) gene (Leiden, Cambridge, Hong Kong; HR2 haplotype) and idiopathic recurrent pregnancy loss (RPL) in Tunisian women. A total of 348 women with RPL, and 203 control women were studied, corresponding to 1,250 pregnancy losses and 1,200 successful pregnancies. FV Leiden was seen in 19.4% of patients (4.3% in the homozygous state) and in 5.5% of controls. The prevalence of the FV HR2 haplotype was similar in patients and controls, but with 7 homozygous patients for 1 control. FV Cambridge and Hong Kong were absent from both patients and controls. The study of all pregnancy losses evidenced that the frequency of the factor V Leiden polymorphism was zero in women who had mis-carried before 7 weeks of gestation, and then sharply increased to a plateau. After categorization of pregnancy losses (before 8 weeks of gestation; weeks 8 and 9; weeks 10 to 12; from the 13th week of gestation onwards), heterozygous and homozygous factor V Leiden polymorphisms, and homozygous FV HR2 haplotype, were associated with significant and independent risks of pregnancy loss during weeks 8 and 9, which increased during weeks 10 to 12, then culminated after week 12. In Tunisian women with idiopathic RPL, factor V Leiden polymorphism and homozygous FV HR2 haplotype are not a risk factor for very early pregnancy loss, before 8 weeks of gestation, but are thereafter associated with significant clinical risks, which gradually increase from the 8th week onwards.