Objective By developing an automatic procedure for optimization of femoro-tibial contact area for knee prosthesis, to summarize the influence pattern of design parameters on contact area, and discover the relationship between the maximum contact stress and contact area. Methods A parametric finite element (FE) model was developed in the Isight software, which included three components: automatic parameter changes for the geometric model, automatic modeling in the FE software, and automatic FE calculation. The automatic workflow was realized, and then contact areas were statistically analyzed. Results The FE model was validated by using Tekscan pressure distribution system. When the femoral sagittal radius was gradually close to the tibial sagittal radius, the contact area gradually reached to the maximum 295 mm2. The femoral sagittal radius had a positive effect on contact area, while the tibial sagittal radius had a negative effect. The maximum contact stress had a linear relationship with contact area approximately. Conclusions This study analyzed the influence of femoro-tibial sagittal radius on contact stress and contact area, and the research findings would provide references for the design on reducing wear of tibial insert in clinic.