Objective To investigate the risk factors of long-term in-stent restenosis (ISR) and its correlation with remnant cholesterol (RC) in coronary heart disease (CHD) with low-density lipoprotein cholesterol (LDL-C) compliance after percutaneous coronary intervention (PCI). Methods A retrospective study was conducted of the clinical data of 239 CHD inpatients in the Department of Cardiology of Yixing People′s Hospital from January 2015 to October 2022. All patients had a previous stent placement and underwent coronary angiography after hospitalization. Fasting blood routine and biochemical indicators were tested on the day following admission. According to the results of coronary angiography, they were divided into ISR group (n=58) and non-ISR group (n=181). SPSS statistics 16.0 was used for data analysis. According to the data types, t test or Chi-square test was used for intergroup comparison. The Spearman correlation was used to analyze the correlation between RC and ISR. Receiver operating characteristic (ROC) curve was drawn to determine the optimal cutoff value of RC. Multivariate logistic regression was used to analyze the risk factors of ISR. Results The two groups showed statistical significant differences in age, total cholesterol (TC), RC, number of stents, total stent length and proportion of diabetes mellitus, smoking and multiple vessel lesions (P<0.05). The RC interquartile range was calculated, and the patients were divided into four groups (Q1-Q4) accordingly with an ISR rate of 20.0%, 14.8%, 22.0%, and 40.7%, respectively, showing statistically significant differences (P<0.05). Further Spearman correlation analysis revealed a positive correlation between RC and ISR (r=0.179; P<0.05). ROC analysis showed an area under ROC curve of 0.636 (95% CI 0.572-0.697; P<0.05) for RC. By calculating the Youden index, the optimal cutoff value for RC was 0.47 mmol/L with a sensitivity of 51.72% and a specificity of 75.14%. Multivariate logistic regression analysis showed that age (OR=1.041,95%CI 1.005-1.078; P＜0.05), smoking (OR=5.797, 95%CI 1.617-20.774; P＜0.05), multiple vessel lesions (OR=3.937,95%CI 1.258-12.326; P＜0.05), total stent length (OR=1.034,95%CI 1.001-1.070; P＜0.05), and RC>0.47 mmol/L (OR=3.416, 95%CI 1.535-7.602; P＜0.05) were risk factors of ISR. Conclusion There is a positive correlation between RC and ISR in CHD patients with LDL-C compliance after PCI, and RC is an independent risk factor of ISR after PCI.