There have been increasing concerns about the structural fatigue resistance of crosslinked UHMWPE devices due to deterioration of certain mechanical properties. However, due to the lack of clear correlation between specific mechanical properties and clinical performance, these concerns remain theoretical. In order to evaluate the potential benefits and risks of various crosslinked polyethylene materials for hip and knee bearing applications, two clinically relevant worst-case scenarios were simulated on functional devices. In the first worst-case scenario, cemented all-poly patellar components were tested under simulated stair-climbing conditions with rotational misalignment. In the second worst-case scenario, metal-backed thin acetabular liners were tested in a hip joint simulator under rim-loading conditions. Various types of crosslinked UHMWPE were prepared according to published process descriptions of commercial materials. While significant levels of volumetric wear reduction were confirmed by both the patellar and hip simulator tests, mixed results were obtained on the structural integrity of the devices. The latter was more significantly affected by the post-irradiation thermal treatment history than by the total dose of irradiation. Re-melting following irradiation led to catastrophic fractures of both rim-loaded liners and rotational-malaligned patellar pegs. The key mechanical property that was positively identified to correlate with the structural fatigue performance of crosslinked polyethylene materials was the ultimate tensile strength, whereas tensile elongation within 250% and 400% range had no effect on structural integrity. However, the results presented in this study should not be misconstrued with respect to the potential clinical performance of irradiation crosslinked and re-melted polyethylene liners with proper designs. In fact, the true outcome of all the crosslinked materials can only be revealed by long-term clinical follow-up.