Pulse wave velocity (PWV), a measurement of arterial stiffness, is predictive of cardiovascular diseases and all-cause mortality. By determining the time-delay of pulse waveforms for a known distance measured in the ultrasound image, local PWV can be calculated. The aim of this study was to evaluate PWV estimation in both healthy and diseased common carotid arteries (CCAs) in vivo. Arterial wall displacements were estimated using speckle tracking on ultrasound radiofrequency (RF) data acquired from 26 young subjects (26 +/- 4 yo) and 51 aged subjects (57 +/- 7 yo). PWVs were estimated separately using diameter distension waveforms (distension PWV), displacement waveforms of anterior (near) wall (anterior PWV) and posterior (far) wall (posterior PWV) at both systolic foot (PWVsf) and dicrotic notch (PWVdn). According to the results, higher precision of PWV estimation was achieved using distension waveforms than using displacement waveforms of anterior or posterior wall. Both distension PWVsf and PWVdn were significantly higher in the aged subjects compared with the young subjects (p < 0.0001), and correlated significantly with relative distension of the CCAs (r = -0.27, p = 0.002 and r = -0.62, p < 0.00001, respectively), indicating the feasibility of the PWV estimation using arterial distension waveforms. In contrast, no significant difference of anterior or posterior PWVs was found between the two groups (all p > 0.01). The aged arteries were further divided into two groups based on the presence or absence of atherosclerotic plaques in the carotid arteries, and distension PWVdn was found to be significantly higher in arteries with visible plaques (8.94 +/- 2.25 m/s) than that in plaque-free arteries (7.35 +/- 1.99 m/s, p = 0.003). The preliminary results indicate that carotid PWV estimation using distension waveforms may be a valuable index for assessment of cardiovascular diseases.