Objective: To evaluate the clinical efficacy and safety of Xinkeshu tablet combined with Bisoprolol tablet in the treatment of angina pectoris of coronary heart disease. Methods: 92 patients with angina pectoris with coronary heart disease were selected from February 2023 to February 2024. The patients were divided into control group and observation group by random number table method, with 46 cases in each group. The control group was treated with bisoprolol tablets; Observation group was given Xinkeshu tablets combined with bisoprolol tablets. The main symptom score, cardiac function [left ventricular ejection fraction (LVEF), cardiac output (CO)], cardiovascular adverse events, acute attack admission and adverse reactions were analyzed and compared between the two groups. Results: After 4 weeks of treatment, the main symptom score of both groups was significantly lower than that before treatment, and the main symptom score of the observation group was significantly lower than that of the control group (P < 0.05). After 4 weeks of treatment, the cardiac function indexes of LVEF and CO in both groups were significantly higher than before treatment, and the values of LVEF and CO in the observation group were significantly higher than those in the control group (P < 0.05). During treatment, the total incidence of cardiovascular adverse events and the incidence of hospitalization due to acute attacks in the observation group were significantly lower than those in the control group (P < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P > 0.05). Conclusion: The application of Xinkesu tablets combined with bisoprolol tablets in the treatment of angina pectoris of coronary heart disease can improve the efficacy, relieve the main symptoms, improve the cardiac function of patients, reduce cardiovascular adverse events and acute attack admission, and do not increase adverse reactions, with high safety.