We hypothesized that oxidation would influence the resistance to fatigue crack initiation and propagation of Ultra-High molecular weight polyethylene (UHMWPE). We subjected tibial insert surrogates (ram extruded GUR 1050) to accelerated aging protocols following ASTM F 2003-00 (14, 21 and 28 days). Subsurface disc specimens from the control and aged materials at each time period were subjected to cyclic small punch loading to failure (modification of ASTM F 2183-02). A significant decrease in fatigue loading was observed, relative to the un-aged controls, starting at three weeks of accelerated aging. Furthermore, SEM examination of the failed aged specimens revealed a network of multiple secondary initiation sites, which was also confirmed by observation with endoscopy, and microCT. Thus, in contrast to the unoxidized highly crosslinked conventional materials evaluated previously, the oxidized materials failed by the initiation and propagation of cracks from numerous initiation sites with the brittle appearance increasing with oxidation time. These results suggest that oxidized UHMWPE exhibits a different fatigue crack initiation and propagation behavior compared to unoxidized virgin, and crosslinked UHMWPE. Future studies will be needed to increase our understanding of the clinically acceptable fatigue properties for new tibial bearing materials, such as highly crosslinked UHMWPEs.