Ultra-high-molecular-weight-polyethylene (UHMWPE) has been the material of choice for bearings in total joint replacements (TJRs) for decades as a result of its excellent wear resistance, chemical inertness, energetic toughness, low friction, and biocompatibility. Utilization of this polymer in orthopedic devices requires oxidation, wear, and fatigue resistance. Balancing these important properties by tailoring processing techniques and modulating microstructural features has been an ongoing endeavor in the field. Research into the clinical applications of UHMWPE has primarily focused on the challenges of wear and oxidation while studies into the realm of fatigue have been more limited. Literature gaps exist in fully understanding the fatigue crack initiation near notches or propagation of small existing flaws in UHMWPE used in TJRs. In particular, the characterization of the fatigue thresholds and near-threshold fatigue behavior of orthopedic grade UHMWPE has yet to be thoroughly explored. In this work, we characterized the fatigue crack arrest threshold of clinically-relevant UHMWPE formulations. Correlations between the fatigue thresholds and bulk mechanical properties as well as microstructural properties were examined across these medical resins. The important role played by crosslinking in influencing the fatigue performance of UHMWPE is highlighted in this study. In addition, it is established that J-integral fracture toughness is the best predictor of fatigue thresholds and could possibly be used as a stand-in metric for fatigue performance if thresholds cannot be directly ascertained. Finally, this study corroborates that the true constitutive parameters best describe the mechanical behavior of UHMWPE.