We examined the deformation behavior of a red blood cell (RBC) in various flow fields to determine whether the extent of RBC deformation is correlated with the shear stress used as a hemolysis index. The RBC model was introduced to a simple shear flow (Couette flow) and to slightly complex flows (unsteady shear flows and stenosed flows). The RBC deformation was assessed by the maximum first principal strain over the RBC membrane and compared with the shear stress. Although the results were consistent under steady Couette flow, this was not the case under unsteady Couette flow or stenosed flow due to the viscoelastic nature of the RBC deformation caused by fluid forces. These results suggest that there is a limitation in accurately estimating the mechanical damage of RBCs solely from a macroscopic flow field, indicating the necessity of taking into account the dynamic deformation of RBCs to provide a better estimation of hemolysis. Copyright © 2013 John Wiley & Sons, Ltd.