Polyurethane foams present a tunable biomaterial platform with potential for use in a range of regenerative medicine applications. Achieving a balance between scaffold degradation rates and tissue ingrowth is vital for successful wound healing, and significant in vivo testing is required to understand these processes. Vigorous in vitro testing can minimize the number of animals that are required to gather reliable data; however, it is difficult to accurately select in vitro degradation conditions that can effectively mimic in vivo results. To that end, we performed a comprehensive in vitro assessment of the degradation of porous shape memory polyurethane foams with tunable degradation rates using varying concentrations of hydrogen peroxide to identify the medium that closely mimics measured in vivo degradation rates. Material degradation was studied over 12 weeks in vitro in 1%, 2%, or 3% hydrogen peroxide and in vivo in subcutaneous pockets in Sprague Dawley rats. We found that the in vitro degradation conditions that best predicted in vivo degradation rates varied based on the number of mechanisms by which the polymer degraded and the polymer hydrophilicity. Namely, more hydrophilic materials that degrade by both hydrolysis and oxidation require lower concentrations of hydrogen peroxide (1%) to mimic in vivo rates, while more hydrophobic scaffolds that degrade by oxidation alone require higher concentrations of hydrogen peroxide (3%) to model in vivo degradation. This information can be used to rationally select in vitro degradation conditions that accurately identify in vivo degradation rates prior to characterization in an animal model.