: Osteoprotegerin (OPG), a soluble glycoprotein found in serum, has been associated with both the presence and severity of atherosclerosis. OPG is regarded as the mediator in the process of vascular endothelial dysfunction. Impaired endothelial function has an intimate link with hypertension (HTN) and is associated with significant morbidity and mortality. This study was to investigate the connection between OPG and endothelial dysfunction in patients having HTN. : There are 102 patients with HTN included. For the purpose of determining the levels of OPG, a commercial enzyme-linked immunosorbent test kit was applied. The vascular reactivity index (VRI), which is assessed via the digital thermal monitoring, provides information on endothelial function. : Ten patients with HTN (9.8%) were classified as having poor vascular reactivity (VRI < 1.0), 46 HTN patients (45.1%) as having intermediate vascular reactivity (1.0 ≤ VRI < 2.0), and 46 HTN patients (45.1%) were classified as having high vascular reactivity (VRI ≥ 2.0). A greater serum OPG level ( < 0.001) and older age ( = 0.022) were linked to impaired vascular reactivity. The estimated glomerular filtration rate ( = 0.196, = 0.048) was positively correlated with VRI values in hypertensive participants, while advanced age ( = -0.222, = 0.025) and the log-transformed OPG level (log-OPG, = -0.357, < 0.001) were negatively correlated with VRI. Serum log-OPG level was shown to be strongly and independently correlated with VRI values in HTN individuals after multivariable forward stepwise linear regression analysis (β = -0.357, adjusted R change = 0.119, < 0.001). : In patients with HTN, serum OPG levels were adversely correlated with VRI and probably had a role in endothelial dysfunction.