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Introduction: Allisartan isoproxil is a novel angiotensin II type 1 receptor antagonist that has been confirmed to lower blood pressure and protect target organs effectively. However, its role in improving endothelial function and vascular damage has not been investigated yet., Methods: Patients with initially diagnosed mild essential hypertension (BP ranging from 140/90 to 159/99 mmHg) with age from 25-75 years were randomly assigned 1:1 to either the allisartan group (allisartan 240 mg/day and lifestyle modification) or the lifestyle modification group and were followed up for 30 days. Flow-mediated dilation (FMD), brachial-ankle pulse wave velocity (baPWV) and endothelial microparticles (EMPs) were measured for evaluation of endothelial function and vascular damage. In addition, we enrolled 36 normotensive individuals as healthy control., Results: Seventy-two mildly hypertensive patients were enrolled in this study. After 30 days of treatment, a significant increase in FMD was observed in the allisartan group (0.9 ± 0.7%, p < 0.001) and remained unchanged in the lifestyle modification group, but the difference between the two groups did not reach statistical significance (p = ns). EMPs, baPWV, SBP and DBP decreased by 251.0 ± 255.9 counts/μl (p < 0.001), 102.8 ± 84.2 cm/s (p < 0.001), 13.20 ± 3.9 mmHg (p < 0.001) and 9.35 ± 2.5 mmHg (p < 0.001), respectively, in the allisartan group, while by 21.3 ± 84.3 counts/μl (p = ns), 0.4 ± 22.0 cm/s (p = ns), 3.2 ± 6.0 mmHg (p < 0.01) and 1.0 ± 2.5 mmHg (p = ns), respectively, in the lifestyle modification group. All of the indexes above achieved statistical significance between the allisartan and lifestyle modification groups (p < 0.05). Besides, after 30 days of allisartan administration baPWV and EMPs were comparable to those measured in the healthy control group, while the difference in SBP, DBP and FMD remained significant between the allisartan and healthy control groups (p < 0.05)., Conclusion: The present study demonstrates for the first time that allisartan isoproxil exerts a favorable effect on improving endothelial function and vascular damage in patients with mild EH, making it a promising drug for management of EH., Clinical Trial Registration: ChiCTR2000032332.