Objective To investigate the association between vesicle-associated membrane protein 8 (VAMP8) gene polymorphisms (rs13426038 and rs10166612) and atherosclerotic cerebral infarction (ACI) in Han Chinese population in Hunan, China.Methods The genotypes of rs13426038 and rs10166612 in VAMP8 gene were determined using polymerase chain reaction-restriction fragment length polymorphism in patients diagnosed with ACI (ACI group) and healthy controls (control group). The genotype and allele frequencies were analyzed by χ² test.Results The genotype distributions at rs13426038 and rs10166612 were in agreement with Hardy-Weinberg equilibrium. In the ACI group, the frequencies of CC, CG, and GG genotypes at rs13426038 were 20.5%, 43.6%, and 35.9%, respectively, and the frequencies of C and G alleles were 42.3% and 57.7%, respectively. In the control group, the frequencies of CC, CG, and GG genotypes at rs13426038 were 15.0%, 49.0%, and 36.0%, respectively, and the frequencies of C and G alleles were 39.5% and 60.5%, respectively. There were no significant differences in genotype and allele frequencies at rs13426038 between the ACI group and the control group (P=0.08, P=0.25). In the ACI group, the frequencies of AA, AG, and GG genotypes at rs10166612 were 92.7%, 6.8%, and 0.5%, respectively, and the frequencies of A and G alleles were 96.1% and 3.9%, respectively. In the control group, the frequencies of AA, AG, and GG genotypes at rs10166612 were 91.8%, 8.2%, and 0%, respectively, and the frequencies of A and G alleles were 95.9% and 4.1%, respectively. There were no significant differences in genotype and allele frequencies at rs10166612 between the two groups (P=0.16, P=0.46).Conclusions The polymorphisms of VAMP8 gene (rs13426038 and rs10166612) may not be associated with ACI in Han Chinese population in Hunan, China.