The synthesis of polyurethane nanocomposite coatings containing 1% to 5% suitably dispersed ZnO by 1-stage polyaddition process in the bulk using 4,4′-methylenebis(cyclohexyl isocyanate), poly(ε-caprolactone)diol, and 1,4-butanediol was performed. Infrared and nuclear magnetic resonance spectra confirmed the structure of obtained polyurethanes. Scanning electron microscope and energy dispersive X-ray analyzer methods showed randomly distributed ZnO in a polyurethane matrix. The differential scanning calorimetry and wide-angle X-ray diffraction patterns were used for the microstructural assessment of the obtained materials. Antimicrobial properties of ZnO and the effect of this modifier on the hydrophobicity of the coatings were demonstrated. The obtained coatings were characterized in terms of the mechanical properties and changes during incubation in a Baxter saline solution.