Background and Objective. In external preparations, types and ratios of additives are not necessarily the same for brand-name drugs and generic drugs. Thus, the physicochemical properties of preparations may differ despite the fact that they contain the same ingredients or additives. This study examined differences in brand-name and generic versions of nadifloxacin (NFX) creams. Material and Methods. Three types of NFX creams (NFX-A, NFX-B, and NFX-C) were used. The viscosity of each preparation was determined, its yield value was calculated, and each preparation was subjected to light microscopy, x-ray powder diffraction, and near-infrared absorption spectroscopy. Results. Comparison of viscosity of different preparations revealed that NFX-B had a lower viscosity than NFX-A and NFX-C (14.5 vs. 24.6 and 17.9 Pa·s). NFX-B also had a lower yield value than NFX-A and NFX-C. Microscopy revealed that NFX-A and NFX-B had satisfactory emulsification although crystallization was observed with NFX-C. Near-infrared absorption spectroscopy revealed changes in the absorption spectra of NFX-B in comparison with those of NFX-A and NFX-C that were due to differences in water content and differences in fat and oil content. Conclusions. These findings confirmed that there were differences in the viscosity and flattening of NFX-A, NFX-B, and NFX-C. In addition, microscopy revealed differences in emulsification and it revealed the precipitation of NFX crystals in NFX-C. Near-infrared absorption spectroscopy revealed that differences in the type and amount of additives and water content in the creams had contributed to differences in the preparations.