Non-invasive evaluation of vascular stiffness has established utility in cardiovascular risk and stroke prediction. This work presents an accelerometric sensor-based system with an integrated hydrostatic pressure correction unit for arterial luminal diameter measurement and local vascular stiffness assessment. A custom-designed accelerometric patch for continuous monitoring of percutaneous acceleration plethysmogram (APG) from the common carotid artery, which could estimate the arterial wall displacement, was developed. A calibration model was established to estimate the true carotid luminal diameter waveform from the accelerometer-based arterial wall displacement signals. The system's accuracy for carotid stiffness measurement was validated by multiple in-vivo human subject studies and compared against a clinical-grade B-mode ultrasound imaging system. Accelerometric-derived carotid diameter waveform morphologically replicated the anachrotic, and dicrotic limb of the true carotid diameter recorded using reference devices. The group-average baseline value of measured carotid end-diastolic diameter and distension was 5.81 ± 0.53 mm and 0.51 ± 0.15 mm with a maximum observed beat-by-beat variation of 6.5% and 9%, respectively. Accelerometer-based vascular stiffness measures showed a significant correlation (R2 > 0.88, P < 0.0001), and clinically acceptable agreement with a reference standard imaging system. APG derived carotid stiffness indices demonstrated the capability to detect expected age-associated changes in stiffness. The study revealed that the accelerometric sensor system offers a reliable, cost-effective method for long-term non-invasive monitoring of location-specific vascular stiffness measures with potential applications in ambulatory healthcare monitors. © 2001-2012 IEEE.