Severe loading and complex kinematics in total knee replacement make wear performance and toughness of the polyethylene in tibial inserts important. We investigated wear of crosslinked polyethylene using a knee simulator and measured toughness using small-punch testing. GUR1050 rods were gamma-irradiated in air at doses from 0 to 200 kGy, annealed in nitrogen, and machined into tibial inserts. The simulator was run to 4 million cycles, and wear rates determined from weight loss. Wear rate decreased by 54, 78, and 95% as radiation dose increased from 50 to 75 to 100 kGy, respectively. At every dose, toughness was significantly less after simulator testing, but the difference between control and wear-tested polyethylene, considered to be due to fatigue damage accumulation, was smallest at 50 kGy. The simulator-tested polyethylene that received 35 to 75 kGy had slightly higher toughness than equivalent material that received no irradiation. However, the toughness of simulator-tested polyethylene that received 150 and 200 kGy was lower than that of the simulator-tested polyethylene that received no irradiation. Our results suggest that an optimal irradiation dose may exist for crosslinked polyethylene for use in TKR and that the optimum dose would be less than the 100 kGy or more that are used in some current crosslinked polyethylene for hip replacement.