The present study examines flow through Bi-Leaflet Mechanical Heart Valves (BMHV) at physiological conditions considering both Newtonian and non-Newtonian fluid models for blood rheology. It is well known that the non-Newtonian effects of blood are pronounced in small diameter arteries. Most of the earlier works on Mechanical Heart Valves (MHV) have considered blood as a Newtonian fluid as the flow involves large-diameter artery such as the aorta. In this work, we have reported the predicted parameters, such as leaflet kinematics, vortex structures, wall shear stress, and blood damage index for both blood models. It is found that the leaflet attributes smaller asynchronous motion in the case of non-Newtonian Carreau fluid model with slightly reduced angular velocity compared to the Newtonian assumption. Predictions on the blood damage index suggest a 21% higher damage while using non-Newtonian model than Newtonian model, which may be attributed to higher levels of mechanical stress within the fluid. However, vortex structures, time-averaged wall shear stress (TAWSS), and oscillatory shear index (OSI) are found to be similar in predictions using both the fluid models. We have used an in-house sharp interface immersed boundary method with fluid–structure interaction to simulate the coupled action of moving valves and pulsatile blood flow. Our findings suggest that the general consensus of using Newtonian model in large arteries may not be appropriate for prediction of leaflet kinematics and blood damage index in Mechanical heart valves.