A medical grade, commercially available polyether urethane, denoted PEU 80A, was exposed to both real time (37 °C) and temperature accelerated (55, 70, and 85 °C) hydrolysis conditions for a period of one year in vitro. Neutral pH and deoxygenated phosphate buffered saline exposure conditions mitigated the well-studied oxidation reaction, allowing for evaluation of hydrolysis events. The hydrolytic sensitivity of the PEU 80A was analyzed using nuclear magnetic resonance (NMR) spectroscopy, liquid chromatography-mass spectrometry (LC-MS), and size exclusion chromatography (SEC). We showed that the only obvious backbone chain scission event occurred at the urethane (carbamate) linkages. Using the widely applied Arrhenius model for accelerated predictions involving chemical reactions, we predict that a 50% reduction in PEU 80A molar mass would require approximately 80 years of exposure at 37 °C in the presence of excess water. The activation energy for urethane linkage hydrolysis of ∼90 kJ mol-1 extracted from this analysis is in agreement with previous reports, where the change in molar mass was accounted for by chain scission events at the urethane linkage. A similar analysis of polydimethylsiloxane (PDMS) modified urethanes PurSil 35 (P35) and ElastEon 2A (E2A), exposed to identical hydrolysis conditions, gave an equivalent activation energy for urethane hydrolysis, indicating that hydrolytic cleavage of backbone urethane linkages is not significantly impacted by the incorporation of PDMS into the urethane structure. However, as previously reported, the activation energy governing the observed molar mass reduction in these PDMS-urethanes is one-third that measured for the hydrolytic chain scission events at the urethane bond. These combined results suggest that the reaction(s) responsible for the observed molar mass changes in the PDMS-urethanes is not due to hydrolytic cleavage at the urethane linkages.