Biocompatible and biodegradable polyurethanes were prepared with fixed aliphatic diisocyanate level and varying ratios of isosorbide, and PCL diol via a simple one-shot polymerization without a catalyst. The successful synthesis of the polyurethanes was confirmed by gel permeation chromatography, (1)H-nuclear magnetic resonance and Fourier transform-infrared spectroscopies and the thermal properties were determined by differential scanning calorimetry and showed glass transition temperatures of around 30-35 °C. The degradation tests were performed at 37 °C in phosphate buffer solution (approx. pH 7.3) and showed a mass loss of around 5 % after 12 weeks, except for the polymer with the highest isosorbide content which showed an initial rapid mass loss. The in vitro cytocompatibility test results following culture of osteoblasts on the polymer surface showed that relative cell number on all of the polyurethane films after 5 days of cultured on polymer films was lower compared to the proliferation rate on the optimized tissue culture plastic. These polymers offer significant promise due to the simplicity of the synthesis and the controlled degradation.