Abstract: Objective To investigate the effect of clopidogrel combined with aspirin in the treatment of patients with coronary heart disease. Methods Totally 360 patients with coronary heart disease were randomly divided into treatment group and control group. The control group was treated with aspirin, and the treatment group was treated with clopidogrel on the basis of the control group. The therapeutic effect, coagulation indexes and adverse reactions were compared between the two groups. Results The total effective rate of the treatment group was 95.56%, which was significantly higher than 87.78% of the control group(P<0.05). After treatment, there were no significant differences in plasma prothrombin time and prothrombin activity between the two groups(P>0.05), but the activated partial thromboplastin time in the treatment group was significantly longer than that in the control group(P<0.05). After treatment, the left ventricular end diastolic diameter of the treatment group was significantly smaller than that of the control group(P<0.05), and the left ventricular ejection fraction was significantly higher than that of the control group(P<0.05). After treatment, the incidence of adverse reactions in the treatment group was 4.44%, which was significantly lower than 11.11% in the control group(P<0.05). Conclusion Clopidogrel combined with aspirin is safe and effective in the treatment of patients with coronary heart disease, which can significantly alleviate the clinical symptoms and promote the recovery of patients.