Background: Coronary artery bypass grafting (CABG) is widely used in the treatment of coronary artery disease. A multicenter, double-blind, randomized, controlled clinical trial was designed to evaluate the efficacy and safety of Huxin Formula post CABG. Patients and Methods: 270 inpatients with coronary heart disease participated in this study. CABG patients in the control group were treated with placebo, while patients in the experimental group were treated with Huxin Formula 1 week after the surgery. All patients were treated for 6 months and followed up for another 6 months. The main outcomes (death, nonfatal myocardial infarction, repeat revascularization, and readmission) were assessed 360 days after treatment, and secondary outcomes (frequency and scores of angina pectoris, etc.) were assessed 0, 90, 180, 270, and 360 days after treatment. Results: Our results showed no significant difference between the 2 groups for the primary endpoints. In patients with cardiac function class II (New York Heart Association), the score of angina pectoris was significantly lower (3.88 +/- 3.86 vs. 5.45 +/- 3.59) and the frequency of angina pectoris attacks was less (0.96 +/- 1.01 vs. 1.36 +/- 0.94) after 90 days of treatment with Huxin Formula compared to placebo (p < 0.05). In patients with 3 coronary vessel lesions, the cardiac function class (1.14 +/- 0.35 vs. 1.05 +/- 0.21) after 360 days was significantly higher in the control group compared to the treatment group (p < 0.05). There were no obvious adverse reactions. Conclusion: Huxin Formula may improve cardiac function of patients with 3 coronary vessel lesions and relieve symptoms of patients with cardiac function class II but failed to show superiority in primary outcomes.