Ultrasound-based algorithms are commonly used to assess mechanical properties of arterial walls in studies of arterial stiffness and atherosclerosis. Speckle tracking based techniques used for estimation of myocardial strain can be applied on vessels to estimate strain of the arterial wall. Previous elastography studies in vessels have mainly focused on radial strain measurements, whereas the longitudinal strain has been more or less ignored. However, recently we showed the feasibility of speckle tracking to assess longitudinal strain of the carotid artery in-silico. The aim of this study was to test this methodology in-vivo. Ultrasound images were obtained in seven healthy subjects with no known cardiovascular disease (39 ± 14 years old) and in seven patients with coronary artery disease (CAD), (69 ± 4 years old). Speckle tracking was performed on the envelope detected data using our previous developed algorithm. Radial and longitudinal strains were estimated throughout two cardiac cycles in a region of interest (ROI) positioned in the posterior vessel wall. The mean peak systolic radial and longitudinal strain values from the two heart cycles were compared between the groups using a student's t-test. The mean peak radial strain was -39.1 ± 15.1% for the healthy group and -20.4 ± 7.5% for the diseased group (p = 0.01), whereas the mean peak longitudinal strain was 4.8 ± 1.1% and 3.2 ± 1.6% (p = 0.05) for the healthy and diseased group, respectively. Both peak radial and longitudinal strain values were thus significantly reduced in the CAD patient group. This study shows the feasibility to estimate radial and longitudinal strain in-vivo using speckle tracking and indicates that the method can detect differences between groups of healthy and diseased (CAD) subjects.