Abstract: Objective To explore the effect of comprehensive intervention on plasma big ET-1 Level in normal middle-aged patients of normal high blood pressure with hypercholesterolemia. Methods Two hundred patients with normal blood pressure were selected as the control group, and 200 patients with normal high blood pressure were selected as the observation group from October 2012 to December 2014 in Zhejiang Hospital. Patients in the observation group were given comprehensive intervention. The levels of triglycerides (TG), total cholesterol (TC), low density lipoprotein (LDL-C), high density lipoprotein (HDL-C) level were measured by automatic biochemical analyzer. The level of plasma big ET-1 was determined by enzyme-linked immunosorbent assay (ELISA). Results The systolic and diastolic blood pressure and the levels of TC, TG, LDL-C, big ET-1 in the observation group were higher than those in the control group (all P<0.05). After intervention, the systolic blood pressure, diastolic blood pressure, TC, TG, LDL-C, and big ET-1 levels at various time points were lower than those before intervention (all P<0.05). With the prolongation of the intervention time, the systolic blood pressure, diastolic blood pressure, TC, TG, LDL-C and big ET-1 levels continued to decrease, and there were statistically significant differences among the time points (all P<0.05). Systolic blood pressure, TC and HDL-C were the influencing factors of plasma big ET-1 (all P<0.05). Conclusion The level of plasma big ET-1 in patients with normal high blood pressure with hypercholesterolemia is significantly higher. Comprehensive intervention can reduce the plasma ET-1 levels of the patients, and has great significance on the prevention of endothelial dysfunction.