Aim To investigate the clinical significance and predictive value of serum carbohydrate antigen 125 (CA125) and brain natriuretic peptide (BNP) in patients with acute myocardial infarction (AMI) and heart failure (HF) occurred during hospitalization. Methods AMI patients admitted to cardiovascular department of Zhengzhou People's Hospital were selected from January to December in 2017. Serum CA125, BNP and color Doppler echocardiography were examined. Cardiac function was assessed within 1 week after coronary artery infusion therapy. The correlation among serum CA125, BNP levels and the indexes of color echocardiography were analyzed. The levels of CA125, BNP and left ventricular ejection fraction (LVEF) in different NYHA cardiac function classification groups of HF patients were compared.Results A total of 124 AMI patients was enrolled, of whom 41 (33.1%) had met the diagnostic criteria for HF. Serum CA125 and BNP levels were negatively correlated with LVEF (r＝－0.227, P＝0.011; r＝－0.569, P＜0.001), and CA125 was positively correlated with BNP (r＝0.270, P＝0.002). The area under curve (AUC) of CA125 predicting HF occurrence after AMI was 0.772 (95%CI 0.679-0.864, P＜0.01), and AUC of BNP was 0.938 (95%CI 0.888-0.988, P＜0.01).Among different NYHA classification groups in 41 patients with HF after AMI, with the increase of NYHA classification, serum levels of CA125 and BNP increased, and LVEF decreased. The differences of CA125, BNP and LVEF among groups were statistically significant (P＜0.001). Conclusion Serum levels of CA125 and BNP have predictive value for the occurrence of HF after AMI, and are correlated with the clinical severity of HF.