The mechanical properties of bone are linked with the orientation. Thus, it is appropriate to model a bone as a transversely isotropic material. In this chapter, the finite element model of a femur with anisotropic materials was implemented with five steps: (1) simulate mechanical testing of a cadaver femur with isotropic material; (2) save the principal stresses and directions of each element from the results of the isotropic model; (3) specify the element coordinate system for each element; (4) define anisotropic material properties of the bone; and (5) modify the material identity numbers in the model. After these steps, ESYSs in the bone model vary across the section and follow the stress principal directions. The developed model with anisotropic materials can be used to simulate the mechanical testing of the bone.