Genetic variations of the scavenger receptor class B type I (SR-BI) have been demonstrated to be associated with plasma lipid parameters, anthropomorphic parameters, and coronary artery disease. We determined the frequency of 3 single-nucleotide polymorphisms within the SR-BI gene (SCARB1) in 354 patients with peripheral arterial disease (PAD) and 354 controls matched for age, sex, and diabetes and related to lipids and disease state, that is, PAD. SCARB1 combined genotype exon 1/intron 5/exon 8 were found to be associated with plasma total and low-density lipoprotein cholesterol levels, respectively. In terms of disease, a significant risk for PAD was observed in female subjects carrying the common allele of exon 8 (odds ratio, 2.623; 95% confidence interval, 1.321-5.208; P=.003). The variant allele of intron 5 was found to be a risk factor for PAD in men (odds ratio, 2.182; 95% confidence interval, 1.288-3.698; P=.005). Furthermore, the SCARB1 combined genotype intron 5/exon 8 proved predictive for PAD in the whole population (P=.006), which remained significant after correction for traditional risk factors. In conclusion, in the present study population, SCARB1 polymorphisms not only show associations with plasma levels of total and low-density lipoprotein cholesterol, respectively, but also with the risk for PAD.