Abstract: Objective To investigate the association between apolipoprotein E (APOE) gene polymorphism and in-stent restenosis(ISR)in patients with coronary heart disease(CHD)after percutaneous coronary intervention(PCI). Methods A total of 172 patients with CHD who underwent drug-eluting coronary stent implantation in the Affiliated Hospital of Xuzhou Medical University from January 2016 to October 2018 and were reexamined by coronary angiography within 36 months were enrolled in this study.According to the results of coronary angiography,the patients were divided into ISR group and non-ISR group.Univariate analysis was used to compare the general data, angiographic features, medication, hematological parameters and APOE genotypes between the ISR group and the non-ISR group. The independent risk factors of ISR were studied by binary logistic regression analysis with the indexes with statistical difference (P＜0.05) as independent variables and ISR as dependent variables. Results Univariate analysis showed that the levels of LDL-C and HbA1c,the frequency of genotype E3/4,the stent length and the number of stents in the ISR group were higher than those in the non-ISR group,while the stent diameter was smaller than that in the non-ISR group (P＜0.05).The level of serum low density lipoprotein cholesterol (LDL-C) in patients with E3/4 genotype was significantly higher than that in the controls.Logistic regression analysis showed that E3/4 genotype, hemoglobin A1c (HbA1c) and LDL-C levels were independent risk factors for ISR. Conclusions Polymorphism of APOE gene is associated with ISR, and E3/4 genotype is an independent risk factor for ISR. Further genetic studies can identify risk genotypes,which is helpful for early prediction and identification of high-risk patients with ISR.