Objective: Factor V G1691A (Leiden), prothrombin G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T mutations are considered risk factors for venous thromboembolism. It remains to be characterized whether the presence of these relatively common mutations poses a risk for peripheral arterial disease (PAD). Therefore, we intended to test, by conducting a case-control study, the hypothesis that PAD was associated with an increased prevalence of factor V G1691A, prothrombin G20210A, and MTHFR C677T mutations., Methods: The study comprised 433 patients admitted for inpatient diagnostics and treatment of PAD in patients with chronic limb ischemia. Patients with acute ischemia or malignancy were excluded. A total of 433 control subjects matched to the patients with PAD in a 1:1 design by sex, age (+/-2 years), and diabetes mellitus status were recruited. Factor V G1691A, prothrombin G20210A, and MTHFR C677T genotypes were assessed by polymerase chain reaction., Results: For the factor V G1691A polymorphism, the genotype frequencies in PAD patients were 92.8% GG (normal homozygotes = wild type) and 7.2% GA (mutant heterozygotes), and in control subjects they were 94.0% GG and 6.0% GA (chi 2 test; P = .493). The distribution of the prothrombin G20210A genotypes was 96.3% GG (normal homozygotes = wild type) and 3.7% GA (mutant heterozygotes) in PAD patients and was 97.2% GG and 2.8% GA in control subjects (chi 2 test; P = .442). Genotype frequencies for the MTHFR C677T polymorphism were 47.8% CC (normal homozygotes = wild type), 43.4% CT (mutant heterozygotes), and 8.8% TT (mutant homozygotes) in PAD patients, compared with 47.1% CC, 44.1% CT, and 8.8% TT in control subjects (chi 2 test; P = .977). Accordingly, as determined by logistic regression analysis, no significant odds ratios for heterozygous or homozygous genotypes of the three polymorphisms could be observed., Conclusions: PAD was not associated with an increased prevalence of factor V G1691A, prothrombin G20210A, and MTHFR C677T mutations in the population studied. Thus, there is no indication that of one of these mutations may be a risk factor for chronic limb ischemia. However, the role of these mutations in acute limb ischemia remains to be clarified.