Receptor of advanced glycation end products (RAGE) is reportedly linked with chronic inflammatory diseases due to aging or diabetes. The aim of this study was to show how −374 T/A RAGE has an impact on systemic vascular damage and renal function. The study subjects were a total of 468 essential hypertension patients from the Non-Invasive Atherosclerotic Evaluation in Hypertension (NOAH) study cohort. We prospectively examined the association of −374 T/A RAGE with their prognoses and investigated the correlation between −374 T/A RAGE and multiple clinical parameters. Kaplan–Meier analysis did not show a significant association of −374 T/A RAGE with total mortality or the prevalence of cardiovascular events. Carriers of the A allele showed a significantly higher prevalence of diabetes mellitus (DM) and lower estimated glomerular filtration rate (eGFR) than subjects without this allele. In subjects with DM, carriers of the A allele showed a significantly lower eGFR. These significant correlations were only seen in male subjects. Carriers of the A allele of −374 T/A RAGE show an independent risk of atherosclerosis and reduced renal function in male hypertensive patients with DM.