Aim To observe the effect of enhanced external counter pulsation (EECP) on endothelial dysfunction and the serum levels of endothelial cell specific molecule-1 (endocan-1) and fat specific serine protease (vaspin) in patients with coronary heart disease (CHD). Methods 200 patients with coronary heart disease who were treated in our hospital from November 2019 to June 2020 were selected as the research objects and randomly divided into control group (n＝98) and observation group (n＝102). The patients in the control group were given conventional drug treatment, and the patients in the observation group were added with EECP for 3 weeks. The therapeutic effect and the changes of vascular endothelial function indexes, serum endocan-1 and vaspin levels before and after treatment were compared between the two groups. Results The proportion of patients with angina relief, increased exercise tolerance, angina pectoris and exercise tolerance in the observation group were 82.35%, 75.49% and 65.69%, respectively, which were significantly higher than 45.92%, 35.71% and 24.49% in the control group (P＜0.05). After 3 weeks of treatment, the angina pectoris attack frequency, duration and total myocardial ischemia load in the observation group were significantly lower than those in the control group (P＜0.05). Flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) in the observation group were significantly increased after treatment, and the increase range in the observation group was significantly higher than those in the control group (P＜0.05). After treatment, serum endocan-1 in the observation group was significantly lower than that before treatment, while serum vaspin was significantly higher, and the changes of serum endocan-1 and vaspin in the observation group were significantly higher than those in the control group before and after treatment (P＜0.05). Conclusions EECP in the treatment of coronary heart disease has a significant effect, it can significantly improve the remission rate of coronary heart disease, improve vascular endothelial function and serum endocan-1, vaspin levels. The changes of serum endocan-1 and vaspin levels may be one of the mechanisms of EECP in protecting vascular endothelial function.