〔Abstract〕 Objective To analyze the influencing factors of in-stent restenosis (ISR) in patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI). Methods A retrospective analysis was conducted on data from 386 patients with CHD admitted to Dongguan Nancheng Hospital from January 2021 to December 2022. All patients underwent PCI treatment by the same surgical team. One year post-procedure, patients were categorized into ISR and control groups based on reexamination results. Relevant patient data, including gender, age, lesion location, family history of CHD, smoking history, hypertension, serum uric acid (SUA) level, high-sensitivity C-reactive protein (hs-CRP) level, number of diseased arteries, diabetes, and stent diameter were compared between the two groups to analyze the risk factors for ISR occurrence after PCI. Results All patients were followed up for one year, revealing 60 cases of ISR, with an incidence rate of 15.54%. The proportions of smoking history, hypertension, SUA level ≥ 380 mmol·L^-1, hs-CRP level ≥ 8 mg·L^-1, diabetes, and stent diameter < 3 mm in the ISR group were higher than those in the control group, with statistically significant differences (P < 0.05). There was no statistically significant differences in gender, age, lesion location, family history of CHD, and number of diseased arteries between the two groups (P > 0.05). Multivariate logistic regression analysis indicated that smoking history, hypertension, SUA level ≥ 380 mmol·L^-1, hs-CRP level ≥ 8 mg·L^-1, diabetes, and stent diameter < 3 mm were independent risk factors for ISR occurrence after PCI (P < 0.05). Conclusion Patients with factors such as smoking history, hypertension, SUA level ≥ 380 mmol·L^-1, hs-CRP level ≥ 8 mg·L^-1, diabetes, and stent diameter < 3 mm have a higher incidence of ISR after PCI. Clinically, proactive preventive measures can be taken targeting these indicators to reduce the occurrence of ISR.