Although the relationship between the local wall shear stresses (WSS) and atheroma development has been previously studied, the effect of variable regional wall distensibility with early atherosclerotic lesions and its effect on local hemodynamics have not been well investigated. We induced early atherosclerotic lesion development in one femoral artery in a Yucatan miniswine model with the contralateral artery serving as control. Eight weeks following atheroma formation, hemodynamic and intravascular ultrasound image data were obtained. Using the measured regional arterial distension as the moving boundary condition, unsteady laminar incompressible computational analysis was performed on the reconstructed arterial segments. With the development of early atherosclerotic lesions, there was increased wall distensibility and an increase in the computed normalized wall shear stress amplitude (NWSA). Alterations in the local fluid mechanics and mass transport at these sites may need to be considered in our understanding of the continued growth of these lesions.