Bone is a highly heterogeneous object. Its composition and structure both vary and depends upon skeletal site, physiological function and age. The goal of this study is to investigate the importance of including material anisotropy in B-Spline based heterogeneous graded (BSBHG) FE model of proximal femur. Five different BSBHG FE models are developed. Out of these five models, four are orthotropic models and one is isotropic model. Each model is simulated in simple stance load condition and their biomechanical response is evaluated and compared with each other as well as those of experimental results given in one of the reference paper for the same specimen in simple stance load condition. The Lagrangian graded element approach is used to assign inhomogeneous isotropic and orthotropic elastic constants in finite element model to improve the performance. Based on the analysis of the two parameters, maximum equivalent Von Mises stress and the displacement in 'z' direction, comparison is achieved. The displacement and Von Mises results have shown that there is small difference between one of the orthotropic model and the isotropic model while the displacement results of the other two orthotropic models show good agreement with the experimental findings. The global strain prediction accuracy for orthotropic model has improved over isotropic model: the regression coefficient increased from 0.63 to 0.9-0.96.