There has been a rising interest in interarm blood pressure difference (IAD), due to its relationship with peripheral arterial disease and its possible relationship with cardiovascular disease. This study aimed to characterize hypertensive patients with a significant IAD in relation to cardiovascular risk. A total of 3699 patients (mean age, 61 ± 11 years) were prospectively enrolled in the study. Blood pressure (BP) was measured simultaneously in both arms 3 times using an automated cuff-oscillometric device. IAD was defined as the absolute difference in averaged BPs between the left and right arm, and an IAD ≥ 10 mm Hg was considered to be significant. The Framingham risk score was used to calculate the 10-year cardiovascular risk. The mean systolic IAD (sIAD) was 4.3 ± 4.1 mm Hg, and 285 (7.7%) patients showed significant sIAD. Patients with significant sIAD showed larger body mass index (P < 0.001), greater systolic BP (P = 0.050), more coronary artery disease (relative risk = 1.356, P = 0.034), and more cerebrovascular disease (relative risk = 1.521, P = 0.072). The mean 10-year cardiovascular risk was 9.3 ± 7.7%. By multiple regression, sIAD was significantly but weakly correlated with the 10-year cardiovascular risk (β = 0.135, P = 0.008). Patients with significant sIAD showed a higher prevalence of coronary artery disease, as well as an increase in 10-year cardiovascular risk. Therefore, accurate measurements of sIAD may serve as a simple and cost-effective tool for predicting cardiovascular risk in clinical settings.