Aseptic loosening from polyethylene debris is the leading cause of failure for metal-on-polyethylene hip implants. The accumulation of wear debris can lead to osteolysis, the degradation of bone surrounding the implant components. In the present study, a parametric three-dimensional finite element model of an uncemented total hip replacement prosthesis was constructed and implanted into a femur model constructed from computed tomography (CT) scan data. Design optimization was performed considering volumetric wear as an objective function using a computational model validated in a previous study through in vitro wear assessment. Constraints were used to maintain the physiological range of motion of wear-optimum designs. Loading conditions for both walking and stair climbing were considered in the analysis. In addition, modification of the acetabular liner surface nodes was performed in discrete intervals to reflect the actual wear and creep damage occurring on the liner surface. Stair climbing was found to produce 49% higher volumetric wear than walking. Using a sensitivity analysis, it was found that the objective function sensitivity to the chosen design variables was identical for both walking and stair climbing. The greatest reduction in volumetric wear achieved while maintaining a physiological range of motion was 16%. It was found that including nodal modification in the sensitivity analysis produced little or no difference in the sensitivity analysis results due to the linear nature of volumetric wear progression. Thus, nodal modification was not used in optimization. An increase in the maximum contact pressure was observed for all wear-optimized designs, and an increase in head-liner penetration was found to be related to a reduction in volumetric wear.