Objective To observe the effect of Qiting Lishui Prescription on the clinical efficacy, quality of life and serum levels of matrix metalloproteinase-2（MMP-2）and matrix metalloproteinase-9（MMP-9）in patients with heart failure of coronary heart disease. Methods 60 patients diagnosed with heart failure of coronary heart disease with Qi deficiency and water retention from September 2018 to September 2019 in cardiovascular department, Beijing Hospital of Traditional Chinese Medicine were randomly divided into control group and treatment group. Both two groups were given standardized treatment by western medicine, the treatment group were treated with extra Qiting Lishui Prescription. The NT-proBNP levels, TCM syndrome score, living quality score and level of MMP-2 and MMP-9 were compared between the two groups of patients.Results The difference of NT-proBNP level before the therapy between the two groups was no significant（P>0.05）. After treatment, the NT-proBNP level of two groups was decreased, the difference was statistically significant（P<0.01）, the NT-proBNP level of the treatment group was much lower than that of the control group, the difference has statistical significance（P<0.05）, and the NT-proBNP decline rate of treatment group was higher than that of the control group, the difference was statistically significant（P<0.01）.There was no significant difference in TCM syndrome score between the two groups before treatment（P>0.05）, while the TCM syndrome score of the two groups after treatment were decreased compared with that before treatment（P<0.05）, and the TCM syndrome score of the treatment group was much lower than that of control group with statistically significant difference（P<0.05）.There was no significant difference in the scores of quality of life before treatment between the two groups（P>0.05）, and the scores of quality of life after treatment were improved compared with that before treatment, with statistically significant difference（P<0.05）. Besides, the scores of quality of life after treatment in the treatment group were higher than those in the control group, with statistically significant difference（P<0.01）. Before treatment, there was no significant difference in MMP-2 and MMP-9 levels between the two groups（P>0.05）. After treatment, MMP-2 and MMP-9 levels of two groups were lower than those before treatment, with statistically significant difference（P<0.05）. After treatment, MMP-2 and MMP-9 levels of the treatment group were lower than that of the control group, with statistically significant difference（P<0.01）.Conclusion Qiting Lishu Prescription can effectively improve the clinical symptoms and quality of life of patients with heart failure of coronary heart disease due to Qi deficiency and water retention, and reduce the levels of NT-proBNP, MMP-2 and MMP-9, suggesting that this prescription may improve the outcomes by alleviating cell matrix damage and myocardial remodeling.