The synthesis of thermoset shape memory polymer (SMP) polyurethanes from symmetric, aliphatic alcohols and diisocyanates has previously demonstrated excellent biocompatibility in short term in vitro and in vivo studies, although long term stability has not been investigated. Here we demonstrate that while rapid oxidation occurs in these thermoset SMPs, facilitated by the incorporation of multi-functional, branching amino groups, byproduct analysis does not indicate toxicological concern for these materials. Through complex multi-step chemical reactions, chain scission begins from the amines in the monomeric repeat units, and results, ultimately, in the formation of carboxylic acids, secondary and primary amines; the degradation rate and product concentrations were confirmed using liquid chromatography mass spectrometry, in model compound studies, yielding a previously unexamined degradation mechanism for these biomaterials. The rate of degradation is dependent on the hydrogen peroxide concentration, and comparison of explanted samples reveals a much slower rate in vivo compared to the widely accepted literature in vitro real-time equivalent of 3% H2O2. Cytotoxicity studies of the material surface, and examination of the degradation product accumulations, indicate that degradation has negligible impact on cytotoxicity of these materials.