Objective: To analyze the risk factors of depression in elderly patients with coronary heart disease (CHD), and to explore the effect of comprehensive nursing care on improvements in depression and quality of life in such patients. Methods: In Phase I of this study, 192 patients admitted to the hospital from May to December, 2016 were selected as subjects, a case-control study was conducted to analyze the risk factors for depression in elderly patients with CHD. In Phase II of this study, 144 patients admitted to the hospital from January to June 2017 were randomized to either comprehensive nursing intervention (primarily cognitive behavioral psychological intervention and continuous nursing) or routine nursing. The effects of comprehensive nursing intervention on depression and quality of life were assessed in the patients. Results: In this study, the prevalence of depression in elderly patients with CHD was 49.0%. Univariate analysis revealed that age, women, education and income levels, course of disease and pain may be associated with depression in elderly patients with CHD. Multivariate logistic regression analysis showed that gender, longer course of disease, lower family income and insomnia were independent risk factors for depression in elderly patients with CHD. The adjusted odds ratios (OR) were 1.87 (95% CI: 1.19 to 2.30), 1.09 (95% CI: 1.04 to 1.1.14), 1.51 (95% CI: 1.17 to 1.86) and 1.94 (95% CI: 1.61 to 2.27), respectively. The improvements in the SDS scores and SF-36 quality of life scores in the comprehensive nursing intervention group were significantly greater than those in the routine nursing group. Conclusion: Women, longer course of disease, low family income and insomnia are independent risk factors for depression in elderly patients with CHD. Comprehensive nursing care results in greater improvements in depression and quality of life of the patients than routine nursing care.