Abstract: Objective To investigate the correlation between serum levels of brain natriuretic peptide (BNP), cancer antigen 125 (CA125) and interleukin-6 (IL-6) with the severity of acute myocardial infarction (AMI) and to evaluate their predictive value for major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI). Methods A total of 100 AMI patients who underwent PCI were enrolled in this study. Patients were divided into MACE group (n=36) and non-MACE group (n=64) based on the occurrence of MACE. Clinical data and serum levels of BNP, CA125 and IL-6 were compared between the two groups. The correlations of serum BNP, CA125 and IL-6 levels with the severity of AMI were analyzed. Factors influencing the occurrence of MACE after PCI in AMI patients were examined. Receiver operating characteristic (ROC) curves were used to assess the predictive value of serum BNP, CA125 and IL-6 for MACE after PCI. Conventional predictive scheme combined risk factors served as the conventional prediction model, while a new prediction model was developed by incorporating serum BNP, CA125 and IL-6 into the conventional model. The area under the curve (AUC), net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used to compare the predictive values of the two models. Results Among the 100 AMI patients, 36 experienced MACE within three months after PCI. The MACE group had significantly higher age, white blood cell (WBC) count, prevalence of prior myocardial infarction and severity of AMI compared to the non-MACE group (P<0.05). Serum levels of BNP, CA125 and IL-6 were significantly higher in the MACE group than in the non-MACE group (P<0.05). Serum BNP, CA125 and IL-6 levels were positively correlated with the severity of AMI (r=0.513, 0.406, 0.320; P<0.05). Age, WBC count, history of myocardial infarction, and serum BNP, CA125 as well as IL-6 were identified as significant predictors for MACE after PCI (P<0.05). The AUC for the combined prediction for MACE using BNP, CA125 and IL-6 was greater than that of each individual marker (Z=2.134, 2.005, 2.087; P<0.05). When age, WBC count and history of myocardial infarction were combined as the conventional prediction model, and serum BNP, CA125 and IL-6 were added to form the new prediction model, the AUC of the new model was significantly higher than that of the conventional model (Z=2.321, P<0.05). Compared with the conventional prediction scheme, the new prediction scheme had both NRI and IDI greater than zero P<0.05). Conclusion Elevated serum levels of BNP, CA125 and IL-6 in AMI patients are associated with the severity of AMI and have predictive value for MACE after PCI. The new prediction model with BNP, CA125 and IL-6 demonstrates superior predictive performance for MACE after PCI compared to the conventional model.