Polymorphic variants of genes encoding blood coagulation proteins have been extensively studied as risk factors for venous or arterial thrombosis A variation in the 3' untranslated region (UTR) involved in the post-transcriptional regulation of factor VII (FVII) gene has been recently identified, a two adenine insertion/deletion at nucleotide 11293. In this study, we investigated its effect on the risk of thrombosis in the frame of two case-control studies, including patients suffering from peripheral arterial disease (PAD) or venous thromboembolic (VTE) disease. The 3'UTR FVII gene polymorphism was investigated i) in 181 patients who had symptomatic atherosclerotic disease of the lower limbs, ii) in 178 patients who had had at least one episode of objectively diagnosed deep venous thrombosis and iii) in controls matched for age and sex. Plasma FVII antigen (FVII: Ag) levels were lower in the presence of the 3'UTR 2A insertion (68.4 +/- 12.3%, 81.3 +/- 14.5% and 89.5 +/- 13.7% in 2A/2A, 2A/0 and 0/0 subjects respectively, p < 0.0001). No significant relationship was found with VTE disease. In the contrary we observed a lower risk of PAD for the 2A/2A compared to the 0/0 genotype after adjustment for traditional risk factors (hypercholesterolemia, smoking status, diabetes and hypertension), with an OR of 0.24 [95% CI 0.06-0.99]. In conclusion, the 2 adenine insertion in the 3'UTR of FVII gene, related to lower plasma FVII levels, is a genetic variation that may contribute to reduce the risk of PAD.