Objective To explore the relationships between systemic immune-inflammation response index (SIIRI) and the severity of coronary artery stenosis and long-term major adverse cardiovascular events (MACEs) in patients with coronary heart disease (CHD). Methods A total of 545 patients admitted to No. 904 Hospital of Joint Logistics Support Force of PLA due to chest pain and underwent coronary angiography from Dec. 2020 to Dec. 2021 were retrospectively enrolled. According to the results of coronary angiography, the patients were divided into CHD group (n=435) and non-CHD group (n=110). According to the Gensini score, the CHD patients were divided into severe coronary artery stenosis group (Gensini score ≥ 30, n=272) and mild coronary artery stenosis group (Gensini score 1-<30, n=163). The SIIRI calculation formula was:SIIRI=neutrophil count×monocyte count×platelet count÷lymphocyte count. The CHD patients were followed up for 1 year and 216 patients were successfully followed up. Based on the follow-up results, the 216 patients were divided into MACE group (n=77) and non-MACE group (n=139). Logistic regression model was used to analyze the independent predictors of CHD and severe coronary artery stenosis. Cox proportional hazard regression model was used to analyze the independent risk factors of MACEs in CHD patients after percutaneous coronary intervention (PCI). Receiver operating characteristic curve was used to analyze the predictive value of SIIRI for severe coronary artery stenosis and MACEs. Results The SIIRI of the CHD group was significantly higher than that of the non-CHD group (305.19×10¹⁸[170.98×10¹⁸, 550.76×10¹⁸]/L² vs 121.25×10¹⁸[91.17×10¹⁸, 194.41×10¹⁸]/L², P<0.001). The ability to predict CHD was the strongest when the SIIRI cutoff value was 251.02×10¹⁸/L², with a sensitivity of 58.9 % and a specificity of 90.9 %. The SIIRI of the severe coronary artery stenosis group was significantly higher than that of the mild coronary artery stenosis group (420.75×10¹⁸[238.76×10¹⁸, 810.13×10¹⁸]/L² vs 185.41×10¹⁸[127.39×10¹⁸, 294.07×10¹⁸]/L², P<0.001). When the SIIRI cutoff value was 304.86×10¹⁸/L², the efficacy of predicting severe coronary artery stenosis was the highest, with a sensitivity of 68.0 % and a specificity of 79.1 %. The SIIRI of the MACE group was significantly higher than that of the non-MACE group (942.38×10¹⁸[528.00×10¹⁸, 1 494.43×10¹⁸]/L² vs 319.93×10¹⁸[176.41×10¹⁸, 498.90×10¹⁸]/L², P<0.001). When the SIIRI cutoff value was 650.23×10¹⁸/L², the predictive ability for MACEs after PCI was the strongest, with a sensitivity of 71.4 % and a specificity of 84.9 %. The values of area under curve for SIIRI in predicting CHD, severe coronary artery stenosis, and MACEs were 0.809 (95 % confidence interval[CI]0.770-0.848), 0.775 (95 % CI 0.732-0.819), and 0.798 (95 % CI 0.732-0.864), respectively, and were all higher than those of systemic immune-inflammation index, systemic inflammatory response index, platelet to lymphocyte ratio, neutrophil to lymphocyte ratio, and monocyte to lymphocyte ratio. Conclusion SIIRI is an independent risk factor of CHD and severe coronary artery stenosis. It also has good predictive value for long-term MACEs in CHD patients after PCI.