Segmented polyurethane multiblock polymers containing polydimethylsiloxane and polyether soft segments form tough and easily processed thermoplastic elastomers. Two commercially available examples, Elast-Eon E2A (denoted as E2A) and PurSil 35 (denoted as P35), were evaluated for molecular and mechanical stability after immersion in buffered water for up to 52 weeks at temperatures ranging from 37 to 85 °C. Dynamic mechanical spectroscopy experiments, performed in tension and shear, were used to characterize the linear viscoelastic properties of compression-molded (dry) specimens. Small-angle X-ray scattering measurements indicated a disorganized microphase-separated morphology for all test conditions. Upon aging in phosphate buffered saline, samples of E2A and P35 were analyzed by size exclusion chromatography (SEC) and tensile testing as a function of time and temperature. The absolute molar mass of each material prior to aging in water was determined by SEC using a multiangle light scattering detector. Aging at 85 °C and 52 weeks lead to a 67% and 50% reduction in molar mass from the original values for E2A and P35, respectively. We attribute the reduction in molar mass to hydrolysis of the polymer backbone and have evaluated the data using a pseudo-zero-order kinetics analysis. The temperature dependence of the extracted rate data is consistent with an activated (i.e., Arrhenius) process, and thus all the molar mass reduction data can be reduced to a single master curve. Concomitant with the reduction in molar mass, E2A and P35 transformed with aging from strain-hardening to strain-softening materials, characterized by substantially reduced tensile strength (stress at failure) and ultimate elongation (strain at failure) relative to the original properties.