Objective To explore the relationship between the levels of serum soluble tumor necrosis factor receptor 1 (sTNFR1) and angiopoietin-like protein 8 (ANGPTL8) and the prognosis of patients with coronary atherosclerotic heart disease (CHD) after percutaneous coronary intervention (PCI). Methods A total of 80 patients with CHD who underwent PCI at Tianyou Hospital, Wuhan University of Science and Technology from April 2022 to October 2023 were selected as the research subjects. According to the occurrence of adverse cardiovascular events within 12 months after surgery, the 80 patients were divided into a good prognosis group and a poor prognosis group. The clinical data and serum sTNFR1 and ANGPTL8 levels of the two groups were compared. Logistic multivariate regression analysis was used to screen the risk factors for poor prognosis after PCI in CHD patients. The ROC curve was used to evaluate the efficacy of serum sTNFR1 and ANGPTL8 in predicting poor prognosis after PCI in CHD patients.Results After clinical assessment, among the 80 included CHD patients, 18 patients (22.50%) had a poor prognosis. Compared with the good prognosis group, the poor prognosis group had higher coronary artery stenosis rate, number of coronary artery lesions, triglyceride (TG), sTNFR1, and ANGPTL8 levels, and the differences were statistically significant (P＜0.05). Logistic regression analysis showed that the number of coronary artery lesions (OR=1.895), sTNFR1 (OR=1.779), and ANGPTL8 (OR=1.747) were independent risk factors for poor prognosis after PCI in CHD patients. The ROC curve showed that the sensitivity of serum sTNFR1 and ANGPTL8 in predicting poor prognosis after PCI in CHD patients was 87.60% and 84.50%, respectively; the specificity was 68.50% and 65.20%, respectively; and the area under the curve was 0.872 and 0.868, respectively. The combined prediction of the two had higher sensitivity (90.50%), specificity (72.60%), and area under the curve (0.905) than the single indicators. Conclusion Serum sTNFR1 and ANGPTL8 are independent influencing factors for poor prognosis after PCI in CHD patients, and their combination has a high predictive efficacy and can be used as sensitive indicators for auxiliary assessment of PCI prognosis