Heart failure (HF) is a serious and terminal stage of various cardiac diseases and the most common complication of coronary heart disease (CHD). Previous clinical studies have shown that Qishen Yiqi dropping pills (QSYQ) have the effect of treating chronic heart failure. This study aims to evaluate the clinical efficacy, safety and optimal effective dose of QSYQ in treating CHD complicating chronic HF with reduced ejection fraction (HFrEF).We will conduct a randomized, double-blind, placebo controlled, multicenter clinical trial. A total of 228 individuals from 16 hospitals in China will be randomly assigned to the low-dose, high-dose, and placebo groups in a ratio of 1:1:1. The trial consists of a screening period (standard medical treatment for at least 2 weeks) and a 12-week treatment period. After randomization, follow-up will be conducted at the 4th, 8th and 12th week. The primary outcomes will be the 6-Minute Walk Test (6MWT) at Week 12. Secondary outcomes will include 6MWT distance at Week 4 and 8, New York Heart Association (NYHA) functional classification, Traditional Chinese Medicine (TCM) Syndrome score, echocardiography indices, N-terminal pro-B-type natriuretic peptide (NT-proBNP), oxyhemoglobin saturation, Minnesota living with heart failure questionnaire (MLHFQ) score, grasp strength body mass index test and cardiovascular adverse events (AE).This trial has been approved by the Research Ethics Committee of the First Affiliated Hospital of Guangzhou University of Chinese Medicine, China (approval number: ZYYEC [2021]005). Written informed consent will be obtained from all participants. The results of this trial will be publicly shared through academic conferences and peer-reviewed journals.Clinical Trials Registry (NCT04983043, Date: 07/08/2021, https://clinicaltrials.gov/ct2/show/NCT04983043).© 2023 He et al.