The effects of inertial loads on the interface stresses between trans-tibial residual limb and prosthetic socket were investigated. The motion of the limb and prosthesis was monitored using a Vicon motion analysis system and the ground reaction force was measured by a force platform. Equivalent loads at the knee joint during walking were calculated in two cases with and without consideration of the material inertia. A 3D nonlinear finite element (FE) model based on the actual geometry of residual limb, internal bones and socket liner was developed to study the mechanical interaction between socket and residual limb during walking. To simulate the friction/slip boundary conditions between the skin and liner, automated surface-to-surface contact was used. The prediction results indicated that interface pressure and shear stress had the similar double-peaked waveform shape in stance phase. The average difference in interface stresses between the two cases with and without consideration of inertial forces was 8.4% in stance phase and 20.1% in swing phase. The maximum difference during stance phase is up to 19%. This suggests that it is preferable to consider the material inertia effect in a fully dynamic FE model.