Haptoglobin (Hp) 2-2 phenotype is a genetic risk factor in coronary atherosclerosis. In this study, haptoglobin phenotypes were determined in 141 patients with peripheral arterial occlusive disease (PAOD) and compared to a reference population (n = 1000). The relative Hp1 allele frequency was decreased among PAOD patients (0.294 vs. 0.403 for the reference population, P < 0.01) due to an overrepresentation of the Hp 2-2 phenotype (50%, odds ratio 1.82 (95% C.I. 1.28-2.60), P < 0.001). This finding was even more pronounced in non-diabetic and in non-smoking PAOD patients (Hp1 allele frequencies: 0.265 and 0.228, respectively). Serum lipids, inflammatory parameters, and blood pressure levels were comparable among the Hp phenotypes, but serum levels of the antioxidant vitamin C were lower in Hp 2-2 patients than in patients with another phenotype (P < 0.05). In PAOD patients with severe atherosclerotic lesions, maximal walking distance of patients carrying a Hp 2-2 phenotype (225-525 m) exceeded that of other Hp phenotypes (50-242 m) (interquartile ranges) (P < 0.05). The findings demonstrate that, despite an increased risk for developing PAOD, the Hp 2-2 phenotype is associated with a longer maximal walking distance which might be attributed to the earlier reported in vitro angiogenic properties of the Hp 2-2 molecule.