In this article, novel antibacterial PVC-based films coated with ZnO nanoparticles (NPs) were fabricated, characterized, and studied for their antibacterial properties. It was shown that the ZnO NPs were coated on the surface of the PVC films uniformly and that the coating process did not affect the size and shape of the NPs on the surface of PVC films. Films coated with concentrations of either 0.2 or 0.075 g/L of ZnO NPs exhibited antibacterial activity against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria, but exhibited no antifungal activity against Aspergillus flavus and Penicillium citrinum. Smaller particles (100 nm) exhibited more potent antibacterial activity than larger particles (1000 nm). All ZnO-coated films maintained antibacterial activity after 30 days in water.