ObjectiveTo explore the clinical efficacy and safety of Qifu Yixin prescription in treating chronic heart failure in the patients with the syndrome of heart Qi deficiency， so as to provide clinical evidence for the treatment of chronic heart failure with this prescription and promote the clinical application and transformation of this prescription. MethodA total of 106 chronic heart failure patients with the syndrome of heart Qi deficiency who met the criteria in Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine （TCM） from September 2022 to May 2023 were selected and randomized into an observation group （53 cases） and a control group （53 cases）. Both groups received routine Western medicine treatment. In addition， the observation group received Qifu Yixin prescription， while the control group received placebo. The treatment course for both groups was 12 weeks. The New York heart association （NYHA） cardiac function grading， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， soluble growth-stimulating expression gene 2 （sST2）， left ventricular ejection fraction （LVEF）， the ratio of early diastolic maximum mitral flow velocity （E） to early diastolic mitral annular motion velocity （e'） （E/e'）， left ventricular end diastolic diameter （LVEDD）， TCM syndrome scores， 6-minute walking test （6MWT）， Minnesota Living with Heart Failure Questionnaire （MLHFQ）， and Kansas City Cardiomyopathy Questionnaire （KCCQ） were determined before and after treatment. ResultFinally， 102 patients were included for analysis， including 51 patients in the observation group and 51 patients in the control group. After treatment， 42 patients in the observation group showed improved cardiac function grading， with a total response rate of 82.35%， and 32 patients in the control group showed improved cardiac function grading， with a total response rate of 62.75%. The total response rate regarding the cardiac function in the observation group was higher than that in the control group （χ²=4.923， P<0.05）. The observation group outperformed the control group in lowering the NT-proBNP level， elevating LVEF， decreasing the E/e' ratio （P<0.05）， reducing LVEDD and sST2 levels， and recovering TCM syndrome score， 6MWT score， MLHFQ score， and KCCQ score （P<0.05）. None of the safety indexes in the two groups showed abnormal values before and after treatment， and no serious adverse reaction was observed. ConclusionQifu Yixin prescription can improve the heart function， exercise tolerance， and quality of life and alleviate the TCM syndrome of the chronic heart failure patients with the syndrome of heart Qi deficiency by inhibiting myocardial fibrosis.