Objective To analyze the correlation of metabolic score for insulin resistance (METS-IR) and triglyceride and glucose (TyG) index with the severity of coronary stenosis in patients with coronary artery disease (CAD) who carry the ε4 allele of apolipoprotein E (ApoE). Methods A retrospective analysis was conducted on 308 patients with coronary heart disease identified by coronary angiography carrying ApoE4 genotypes ε3ε4 and ε4ε4 admitted in Affiliated Hospital of Xuzhou Medical University from January 2021 to December 2022. Their clinical data were collected, and TyG index and METS-IR were calculated. According to the results of modified Gensini score (GS) of 2019 for CAD stenosis, they were divided into low (n=106), intermediate (n=100), and high GS (n=102) groups. SPSS statistics 27.0 was used for statistical analysis. One-way analysis of variance, Kruskal-Wallis H test, or Chi-square test was employed for intergroup comparison depending on data type. Logistic regression analysis was applied to explore the influencing factors for severity of CAD stenosis in patients carrying the ApoEε4 allele. Spearman correlation analysis was performed to analyze the correlation of METS-IR and TyG index with GS. Receiver operating characteristic (ROC) curve was plotted and Delong test was conducted to compare the predictive value of METS-IR and TyG index for the severity. Results METS-IR were significantly higher in the high GS group than in the other two GS groups, and TyG in high GS group was significantly higher than that in low GS group(P<0.05). Spearman correlation analysis indicated a positive correlation of METS-IR and TyG index with GS (r=0.210,0.658; P<0.001). Logistic regression analysis showed that METS-IR was an independent predictor of stenosis severity in CAD patients carrying ApoEε4 allele (OR=1.147,95%CI 1.077-1.221; P<0.001). ROC curve analysis revealed that the area under the curve of METS-IR and TyG index in prediction for coronary stenosis in the CAD population with ApoEε4 allele was 0.824 and 0.608, respectively, and METS-IR had better performance. Conclusion METS-IR is superior to TyG index in prediction for severity of coronary stenosis in ApoEε4 allele CAD patients.