Novel poly(dimethylsiloxane)-based polyurethane nanocomposites (TPU-NCs) were synthesized using in situ polymerization with the nanoclay Cloisite 30B. Differential scanning calorimetry, thermogravimetric analysis, and dynamic mechanical thermal analysis showed that TPU-NCs with an organoclay content of <= 5 wt % exhibited increased thermal stability, storage modulus, and hard-segment melt temperatures but decreased degrees of crystallinity. TPU-NCs displayed increased surface hydrophilicity and enhanced surface free energy with increasing organoclay content. Small and wide-angle X-ray scattering confirmed intercalated formations of organoclays in the nanocomposites. Individual clay particles on the surfaces of TPUs with lower organoclay loadings (1 or 3 wt %) or organoclay agglomerates in TPUs with higher amounts of organoclay (>= 5 wt %) were detectable using scanning electron microscopy. The relatively smooth and homogeneous character of pure TPU and the distinctly heterogeneous and rough surfaces of TPU-NCs were detected via atomic force microscopy. Among the nanomaterials prepared, TPU-NCs with 1 wt % organoclay provided the best balance between the organoclay concentration and the functional properties desired in biomedical applications.