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Objective: To evaluate the effect of Qishen granule (QSG) on heart failure (HF) and the potential mech-anisms involved in animal models. Methods: Studies of QSG in animals with HF were identified by searches of eight databases up to August 1, 2019. Two authors independently reviewed each study and the Collaborative Approach to Meta-analysis and Review of Animal Data from Experimental Studies 10-item checklist was used for quality assessment. The primary outcomes were indicators of left ventricular ejection fraction and/or left ven-tricular fractional shortening. The secondary outcome measures were ventricular structure, hemody-namics, myocardial injury-related indicators, and the mechanisms whereby QSG ameliorates HF. A meta-analysis was performed and all the data were analyzed using RevMan 5.3 software. Results: Thirteen studies containing a total of 240 animals met the criteria for the meta-analysis. The quality score of the studies ranged from three to six points. The meta-analysis showed a significant effect of QSG to improve cardiac function, inhibit ventricular remodeling, improve circulation, and attenuate myocardial injury. The possible mechanisms was identified to be suppression of the renin-angiotensin-aldosterone system, which has anti-fibrotic, anti-apoptotic, anti-inflammatory, and anti-oxidative effects in the myocardium, the prevention of calcium overload, and the promotion of myocardial energy metabolism. Conclusion: Our review shows that QSG has a cardioprotective effect in animal models of CHF. However, due to the relatively poor quality of the included studies and the differences between humans and an-imal models, the results should be interpreted with caution.