To get a clear picture of the pulsatile nature of blood flow and its role in the pathogenesis of atherosclerosis, a comparative study of blood flow in large arteries is carried out using the two widely used models, McDonald’s and Burton’s models, for the pressure gradient. For both models, the blood velocity in the lumen is obtained analytically. Elaborate investigations on the wall shear stress (WSS) and oscillatory shear index (OSI) are carried out. The results are in good agreement with the available data in the literature. The superiority of McDonald’s model in capturing the pulsatile nat re of blood flow, especially the OSI, is highlighted. The present investigation supports the hypothesis that not only WSS but also OSI are the essential features determining the pathogenesis of atherosclerosis. Finally, by reviewing the limitations of the present investigation, the possibility of improvement is explored.