Objective: To investigate the mechanism of factor-alpha-related protein 9 (CTRP9) in mitigating the vascular endothelial cell (VEC) injury in patients with hypertensive heart disease (HHD) by the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) axis. Methods: 43 patients with HHD admitted to our hospital from February 2018 to February 2019 were included in the study group, and another 39 healthy controls from the same period were the reference group. The total protein of transfected VECs was detected by western blotting, and the proliferation rate of the VECs was determined by Cell Counting Kit-8 (CCK-8). The levels of CTRP9, high sensitivity C-reactive protein (hs-CRP), thrombomodulin (TM), and von Willebrand factor (vWF) were detected by ELISA. The mechanism of CTRP9 in alleviating VEC injury in HHD patients by inhibiting the PI3K/Akt/mTOR axis was analyzed. Results: The two groups did not differ in terms of their general data (P>0.05). The CTRP9 level in the study group was higher than in the reference group (P