Metallic femoral components with ceramic articulating surfaces can substantially lower polyethylene (PE) wear during walking activities under conditions of normal knee alignment. It is unknown whether these types of components can maintain low wear rates under conditions of knee malalignment and the harsher kinematics associated with younger, athletically active patients. Wear was measured in non–cross-linked, ethylene oxide–sterilized PE inserts against oxidized zirconium or cobalt-chrome femoral components in a knee wear simulator. The vertical load was modified to replicate knee varus malalignment of 3°, and the range of tibial rotation was increased to 20°. Mean gravimetric and volumetric wear rate over 5 million cycles was 55% lower in the oxidized zirconium group. An oxidized zirconium femoral component can significantly reduce PE wear under simulated conditions of athletically active patients with modestly malaligned total knee arthroplasty prostheses.