Arteries experience marked variations in blood pressure and flow during the cardiac cycle that can intensify during exercise, in disease, or with aging. Diverse observations increasingly suggest the importance of such pulsatility in arterial homeostasis and adaptations. We used a transverse aortic arch banding model to quantify chronic effects of increased pulsatile pressure and flow on wall morphology, composition, and biaxial mechanical properties in paired mouse arteries: the highly pulsatile right common carotid artery proximal to the band (RCCA-B) and the nearly normal left common carotid artery distal to the band (LCCA-B). Increased pulsatile mechanical stimuli in RCCA-B increased wall thickness compared with LCCA-B, which correlated more strongly with pulse (r* = 0.632; P < 0.01) than mean (r* = 0.020; P = 0.47) or systolic (r* = 0.466; P < 0.05) pressure. Similarly, inner diameter at mean pressure increased in RCCA-B and correlated slightly more strongly with a normalized index of blood velocity pulsatility (r* = 0.915; P < <0.001) than mean flow (r* = 0.834; P < 0.001). Increased wall thickness and luminal diameter in RCCA-B resulted from significant increases in cell number per cross-sectional area (P < 0.001) and collagen-to-elastin ratio (P < 0.05) as well as a moderate (1.7-fold) increase in glycosaminoglycan content, which appears to have contributed to the significant decrease (P < 0.001) in the in-vivo axial stretch in RCCA-B compared with LCCA-B. Changes in RCCA-B also associated with a signficant increase in monocyte chemoattractant protein-1 (P < 0.05) whereas LCCA-B did not. Pulsatile pressure and flow are thus important stimuli in the observed three-dimensional arterial adaptations, and there is a need for increased attention to the roles of both axial wall stress and adventitial remodeling.