Background:The objective was to explore the value of serum carbohydrate antigen 125 (CA125) combined with N-terminal pro B-type natriuretic peptide (NT-proBNP) in predicting the clinical prognosis of patients with acute heart failure (AHF). Methods:We prospectively observed 213 patients with AHF. CA125 (U/ml) and NT-proBNP (pg/ml) were dichotomised based on ROC curve analysised prognostic cutpoints, and a variable with four groups was formed (CA125 and NT-proBNP): C1 = CA125 < 47.6 and NT-proBNP <3790 (n = 100); C2 = CA125 < 47.6 and NT-proBNP >= 3790 (n = 29); C3 = CA125 >= 47.6 and NT-proBNP < 3790 (n = 26); C4 = CA125 >= 47.6 and NT-proBNP >= 3790 (n = 58). Kaplan-Meier curve was drawn and multivariate COX regression analysis was performed to analyse the prognostic efficacy of CA125 combined with NT-ProBNP in patients with AHF. Results:The levels of CA125 and NT-proBNP in death group were obviously higher than those in non-death group [56.20 (45.70, 78.00) vs 31.10 (19.48, 47.68),p < 0.001; 5619.00 (2924.00, 10066.00) vs 2203.00 (1460.50, 5070.25),p < 0.001]. The ROC curve showed that the best cut-off values of CA125 and NT-proBNP for predicting the prognosis of AHF were 47.6 and 3790, respectively. Multivariate COX regression analysis showed that CA125 >= 47.6 and NT-proBNP >= 3790 were independent predictors of 1-year all-cause death in patients with AHF (HR = 3.05, 95%CI: 1.50-6.20,p = 0.002) and (HR = 2.34, 95%CI: 1.19-4.61,p = 0.014). At 12 months, 55 deaths (25.8%) were identified. The cumulative rate of mortality was highest for patients in C4 (56.9%), intermediate for C2 and C3 (24.1% and 34.6%, respectively), and lowest for C1 (6.0%), andp-value for trend <0.05. After adjusting for established clinical risk factors, compared with C1: C2 (HR = 4.58, 95%CI: 1.53-13.77,p = 0.007), C3 (HR = 5.24, 95%CI: 1.85-14.82,p = 0.002), C4 (HR = 7.75, 95%CI: 3.09-19.45,p < 0.001). Conclusion:Elevated CA125 is an independent predictor of poor prognosis in patients with AHF, and combined with NT-proBNP can improve the efficiency of risk identification.