OBJECTIVE. Recent study suggested that the genetic polymorphisms of serum amyloid A protein (SAA) were linked to cardiovascular disease (CVD). However, the relationship between genetic polymorphisms of SAA and ankle-to-brachial index (ABI) in healthy subjects has not been studied. We investigated the role of the SAA1 gene polymorphisms with ABI. METHODS AND RESULTS. All participants were selected from a cohort of healthy subjects participating in the Cardiovascular Risk Survey (CRS) study. Four single-nucleotide polymorphisms (SNPs; rs12218, rs4638289, rs7131332 and rs11603089) were genotyped by use of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. There was significant difference between CC genotype and CT genotype [(1.066 ± 0.113) vs (1.119 ± 0.096), p = 0.008], CC genotype and TT genotype [(1.066 ± 0.113) vs (1.127 ± 0.095), p = 0.002] of rs12218 in ABI, and these differences remained significant after adjustment for the sex, age, blood pressure, BMI, alcohol intake, smoking and high-density lipoprotein (HDL) [(1.073 ± 0.018) vs (1.122 ± 0.007), p = 0.012; (1.073 ± 0.018) vs (1.124 ± 0.006), p = 0.009), respectively]. These relationships were not found in rs874957, rs7950019 and rs11603089 before and after multivariate adjustment. CONCLUSIONS. CC genotype of rs12218 in the SAA1 gene was associated with decreased ABI in Chinese Han subjects, which indicated that the carriers of CC genotype of rs12218 have high risk of peripheral arterial disease.