The evaluation of contact areas and pressures in total knee prosthesis is a key issue to prevent early failure. The first part of this study is based on the hypothesis that the patterns of contact stresses on the tibial insert of a knee prosthesis at different stages of the gait cycle could be an indicator of the wear performances of a knee prosthesis. Contact stresses were calculated for a mobile bearing knee prosthesis by means of finite element method (FEM). Contact areas and stresses were also measured through in vitro tests using Fuji Prescale film in order to support the FEM findings. The second part of this study addresses the long-term structural integrity of metal tibial components in terms of fatigue life by means of experimental tests and FEM simulations. Fatigue experimental evaluations were performed on Cr-Co alloy tibial tray, based on ISO standards. FEM models were used to calculate the stress patterns. The failure risk was estimated with a standard fatigue criterion on the basis of the results obtained from the FEM calculations. Experimental and computational results showed a positive matching.