To analyze the polymorphism distribution of the Apolipoprotein E (ApoE) gene in large artery atherosclerosis (LAA)-subtype ischemic stroke (IS) patients in Wuhan. Methods: One-hundred and seventy-nine patients of LAA-subtype IS and 104 healthy controls were selected from the Department of Neurology, Renmin Hospital of Wuhan University. The polymerase chain reaction (PCR)-fluorescence probe technique was used to detect peripheral blood samples from the stroke group and the control group. The differences in the ApoE genotypes and the allele frequency were statistically analyzed. The levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL), and 1ow density lipoprotein cholesterol (LDL) in the different allele sub-groups were compared between the two groups. Results: The frequency of the ε 3/ε 3 genotype was the highest in both the stroke group and the control group. The ε 3/ε 3 genotype frequency of the control group was higher than that of the stroke group (P<0.05). The distribution of ε3/ ε4 and ε4/ε4 genotypes in the stroke group was higher than that in the control group (P<0.05). Compared with the control group, the frequency of ε4 allele was significantly increased and that of the ε3 allele was significantly decreased in the stroke group (P<0.05). There was no significant difference in the distribution of ApoE genotypes among stroke patients with different genders (P>0.05). In the control group, the levels of TC, TG, and LDL of the ε4 phenotype were higher than those of the ε2 and ε3 phenotypes (P<0.05 or P<0.01). In the stroke group, the level of TC in ε4 phenotype was significantly higher than that in the ε2 and ε3 phenotypes (P<0.01), and the level of LDL in the ε4 phenotype was significantly higher than that in the ε2 phenotype (P<0.01). Conclusion: The polymorphic distribution of ApoE in the LAA-subtype IS in the Wuhan area is independent with sex but does affect the levels of blood lipid; ε 4 may be one of the susceptibility factors and risk factors for the LAA-subtype IS