Objective: To explore the relationship between serum creatine kinase isoenzyme (CK-MB) and troponin (CTN) T levels and severity of chronic heart failure (CHF) and clinical prognosis. Methods: The clinical data of 240 CHF patients who were admitted to the department from February 2017 to June 2018 were collected. According to cardiac function grading of New York Heart Association (NYHA), there were 66 cases at grade II, 98 cases at grade III, and 76 cases at grade IV. The CK-MB and cTnT levels were measured after admission. All were given standardized treatment. After discharge, follow-up was conducted to statistically analyze prognosis. Results: Pearson analysis showed that serum CK-MB and CTnT levels were positively correlated with cardiac function grading, left ventricular Tei index and B-type natriuretic peptide (BNP), while negatively correlated with left ventricular ejection fraction (LVEF) (P<0.05). The median follow-up time of 240 patients was 19 months. There were 65 cases of re-admitted due to HF aggravation, and 11 cases with cardiac death. There were 76 case (31.67%) with poor prognosis. Cox multivariate regression analysis showed that cardiac function grading, LVEF, left ventricular Tei index, BNP, CK-MB and CTnT were risk factors for poor prognosis (P<0.05). Conclusion: Serum CK-MB and cTnT are closely related to the severity and clinical prognosis of CHF patients, which can be used as key clinical monitoring indicators.