Abstract: Objective To investigate the clinical effect of sertraline combined with psychotherapy in the treatment of coronary heart disease (CHD) complicated with depression, evaluate the degree of depression and provide scientific basis for clinical treatment. Methods Ninety-one patients admitted to our hospital from July, 2014 to April, 2016 were randomly divided into observation group (n=46) and control group (n=45).The control group received CHD conventional therapy and psychological intervention, while the observation group received additional sertraline treatment on the basis of the control group.The clinical efficacy, SDS, HAMD and SCL-90 score were compared between the two groups.SPSS 17 was used for statistical analysis. Results The total effective rate of the observation group was 97.83% (45/46), which was significantly higher than that of 86.67% (39/45) in the control group (Z=2.496, P=0.013).After 2 and 12 weeks of treatment, the HAMD and SDS scores of the two groups were significantly decreased (P < 0.05), and the observation group was significantly lower than that of the control group (P < 0.05).By SCL-90, the somatization, depression, anxiety, hostility, terror and paranoid scores were all significantly decreased after 2 weeks of treatment (P < 0.05), and 8 indicators continued to decline after 12 weeks of treatment (P < 0.05).There were statistical differences in somatization, depression, anxiety and phobia scores after 12 weeks of treatment in the control group (P < 0.05).The scores of somatization, depression, anxiety and terror in the observation group were significantly lower than those in the control group (P < 0.05). Conclusion It has a significant clinical efficacy of sertraline combined with psychotherapy in the treatment of coronary heart disease complicated with depression.It can effectively reduce the HAMD, SDS and SCL-90 score, and improve the depressive symptoms.It is worthy of popularization and application.