Abstract: Objective To investigate the diagnostic value of nitric oxide (NO), endothelin-1 (ET-1) and homocysteine (Hcy) combined detection in coronary heart disease. Methods A total of 232 coronary heart disease patients as observation group were selected from March 2017 to September 2017 in our hospital, and 128 healthy subjects as control group. The levels of NO, ET-1 and Hcy in the two groups were compared. The detection value of NO, ET-1, Hcy and combined detection of NO, ET-1 and Hcy to coronary heart disease were compared by using the area (AUC) under the receiver operator characteristics curve (ROC). The univariate analysis and logistic regression analysis were used to analyzed risk factors affecting coronary heart disease. Results The level of NO in the observation group was significantly lower than that in the control group, but the level of ET-1 and Hcy in the observation group was significantly higher than those in the control group (all P<0.05). The AUC value of combined detection is significantly higher than the AUC value of NO, ET-1 and Hcy alone (all P<0.05). The incidence of hypertension, diabetes, dyslipidemia, smoking and obesity in the observation group was significantly higher than that in the control group (all P<0.05). Whether as the coronary heart disease as dependent variable, the high blood pressure, diabetes, dyslipidemia, smoking, obesity and ET-1, Hcy, NO as independent variables, multivariable logistic regression analysis, the results showed that the factors in addition to hypertension, dyslipidemia, smoking, obesity, ET-1, Hcy, NO also could be used as evaluating a risk factor for coronary heart disease (all P<0.05), and the correlation strength with coronary heart disease from high to low is ET-1, Hcy, NO. Conclusion The combined detection of NO, ET-1 and Hcy can effectively diagnose the occurrence of coronary heart disease, and it can be used as an effective indicator of the risk of coronary heart disease attack.