Thermoplastic polyurethane (TPU)/organoclay nanocomposites are prepared through a melt extrusion process. The TPU is combined with four differently modified organoclays, namely, I.28E, I.30P, I.34TCN, and I.44P. Wide-angle X-ray diffraction and transmission electron microscopy results show that the addition of I.34TCN and I.30P to TPU/organoclay nanocomposites results in the nearly exfoliated structures of the nanocomposites. Addition of I.28E leads to partially intercalated nanocomposites, whereas I.44P cannot disperse effectively in the nanocomposites. Organoclay can enhance the mechanical and gas barrier properties of TPU. The enhancement follows the order TPU/I.34TCN a parts per thousand yen TPU/I.30P > TPU/I.28E > TPU/I.44P, which is consistent with the degree of dispersion and exfoliation of silicate layers. In addition, Fourier transform infrared absorption spectra show that more hydrogen bonding sites are introduced between the clay modifiers and TPU chains in the TPU/I.34TCN and TPU/I.30P nanocomposites; this has a positive impact on the dispersion of the organoclay and, consequently, the mechanical and gas barrier properties of the nanocomposites.