The relative chemical stability of two commercially available polyurethanes-Pellethane, currently used in biomedical devices, and Corethane, considered as a potential biomaterial-was investigated following aging protocols in hydrolytic and oxidative conditions (HOC, water, hydrogen peroxide, and nitric acid) and in physiological media (PHM, phosphate buffer, lipid dispersion, and bile from human donors). The chemical modifications induced on these polymers were characterized using differential scanning calorimetry (DSC), gel permeation chromatography (GPC), and Fourier transform infrared spectroscopy (FTIR). With the exception of nitric acid, all of the aging media promoted a mild hydrolytic reaction leading to a slight molecular weight loss in both polymers. When aged in water and hydrogen peroxide, Pellethane experienced structural modifications through microdomain phase separation along with an increase of the order within the soft-hard segment domains. The incubation of Pellethane in nitric acid also resulted in an important decrease of the melting temperature of its hard segments with chain scission mechanisms. Moreover, incubation in PHM led to an increase of the order within shorter hard-segment domains. FTIR data revealed the presence of aliphatic amide molecules used as additives on the Pellethane's surface. The incubation of Corethane under the same conditions promoted an almost uniform molecular reorganization through a phase separation between the hard and soft segments as well as an increase of the short-range order within the hard-segment domains. Incubation of this polymer in nitric acid also resulted in a chain scission process that was less pronounced than that measured for the Pellethane samples. Finally, lipid adsorption occurred on the Corethane sample incubated in bile for 120 days. Overall data indicate that polycarbonate urethane presents a greater chemical stability than does polyetherurethane.