Abstract Biodegradable segmented polyurethanes (BSPUs) were prepared with poly(caprolactone) as a soft segment, 4,4′-methylene bis (cyclohexyl isocyanate) and either butanediol (BSPU1) or dithioerythritol (BSPU2) as a chain extender. BSPU samples were characterized in terms of their physicochemical properties and their hemocompatibility. Polymers were then degraded in acidic (HCl 2 N), alkaline (NaOH 5 M) and oxidative (H 2O 2 30 wt.%) media and characterized by their mass loss, Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray diffraction (XRD) and scanning electron microscopy (SEM). Undegraded BSPU1 and BSPU2 exhibited different properties, such as the glass transition temperature T g of the soft segment (−25 vs. 4 °C), mechanical properties (600% vs. 900% strain to break) and blood coagulating properties (clotting time = 11.46 vs. 8.13 min). After acidic and alkaline degradation, the disappearance of the 1728 cm −1 band of polycaprolactone (PCL) on both types of BSPU was detected by FTIR. However, the oxidative environment did not affect the soft segment severely as the presence of PCL crystalline domains were observed both by DSC (melting temperature T m = 52.8 °C) and XRD (2 θ = 21.3° and 23.7°). By TGA three decomposition temperatures were recorded for both BSPU samples, but the higher decomposition temperature was enhanced after acidic and alkaline degradation. The formation of the porous structure on BSPU1 was observed by SEM, while a granular surface was observed on BSPU2 after alkaline degradation.