Background and objective Hypertension (HT)-mediated organ damage (HMOD) refers to structural or functional damage in organs caused by chronic HT, which plays a critical role in determining cardiovascular mortality risk. Traditional ambulatory blood pressure monitoring (ABPM) parameters have limited utility in predicting its occurrence. To address this gap, we focused on indices that reflect blood pressure (BP) variability and arterial stiffness, such as average real variability (ARV), ambulatory arterial stiffness index (AASI), and pulse pressure index (PPI). This study aimed to examine the ability of these novel ABPM-derived indices to enhance the prediction of HMOD. Methods Seventy-nine hypertensive patients were assessed for end-organ damage in the heart, retina, and kidneys. Cardiac involvement was evaluated using echocardiography, focusing on left ventricular mass index (LVMI), relative wall thickness, and diastolic function. Patients with left ventricular hypertrophy (LVH) or diastolic dysfunction were considered to have hypertensive cardiomyopathy. Retinal damage was assessed via fundoscopic examinations, identifying changes like hemorrhages and arterial narrowing. Renal involvement was determined based on the estimated glomerular filtration rate (<
60 mL/min/1.73 m²) and albuminuria (>
30 mg/g). Patients were classified into HMOD and non-HMOD groups based on these criteria. ABPM was conducted to measure traditional parameters, such as 24-hour systolic BP (SBP) and diastolic BP (DBP), and novel indices like ARV, AASI, and PPI. Regression analysis, including demographic characteristics such as age and gender, was also used to evaluate the independent predictive value of ARV, AASI, and PPI. Results Traditional ABPM parameters, including 24-hour BP, did not significantly differ between patients with and without HMOD. However, novel indices such as ARV, AASI, and PPI were significantly higher in the HMOD group and showed stronger predictive value. ARV (OR: 2.026, 95% CI: 1.294-3.171, p=0.002), AASI (OR: 4.950, 95% CI: 1.840-13.317, p=0.002), and PPI (OR: 1.209, 95% CI: 1.081-1.352, p=0.001) emerged as independent predictors of HMOD. Conclusions ARV, AASI, and PPI were found to independently predict HMOD, providing a useful tool for better risk assessment in hypertensive patients. These results suggest that novel ABPM indices could improve early detection and management of HMOD. Further research involving larger and more diverse populations is needed to confirm these findings and guide clinical use.