Objective To investigate the assessment value of serum soluble growth stimulation expressed gene 2 (sST2), N-terminal pro-brain natriuretic peptide(NT-proBNP) and ceramide test (CERT) score combined with Fried frailty scale in evaluating the prognosis of chronic heart failure (CHF) in elderly patients. Methods A retrospective study was conducted on the 304 elderly CHF patients who were hospitalized in the Affiliated Hospital of Xuzhou Medical University from July 2020 to July 2021. According to whether major adverse cardiovascular events (MACE) occurred during the follow-up period of 1 year, they were divided into MACE group(76 cases) and non-MACE group(288 cases). The serum sST2, NT-proBNP, CERT score and frailty status were compared between the two groups. SPSS statistics 25.0 was used for data analysis. Based on the data type, student′s t test, rank sum test or Chi-square test was employed for intergroup comparison. Spearman correlation was applied to analyze the correlation of left ventricular ejection fraction (LVEF) with sST2, NT-proBNP, CERT score and other indicators. The influencing factors of MACE were analyzed by logistic regression analysis. Receiver operating characteristic (ROC) curve was drawn to analyze the prognostic value of serum sST2, NT proBNP, CERT scores and frailty status in elderly CHF patients. Results Serum sST2, NT-proBNP and CERT score were negatively correlated with LVEF (r=-0.241, -0.193, -0.183; P<0.05). The MACE group had higher sST2, NT-proBNP and CERT score, larger proportion of frail patients, and lower LVEF when compared with the non-MACE group (P<0.05). ROC curve analysis showed that the area under the curve (AUC) of poor prognosis of CHF patients predicted by serum sST2, NT-proBNP, CERT scores and frailty were 0.695,0.713,0.636 and 0.658, respectively, and the AUC of combined prediction was 0.800. Conclusion Serum sST2, NT-proBNP, CERT score and frailty are important factors affecting the occurrence of MACE in elderly patients with CHF. They have high prognostic value, and even higher prognostic value when combined together.