Objective: In this study, the influence of several parameters that could impact the use of titanium dioxide nanotubes as cefuroxime carriers was investigated. Method: Cefuroxime loading and release was studied for 90 min with three nano-topography conditions (nano-smooth, nano-rugged and nano-tubular), two cefuroxime loading solution concentrations (150 mg/mL and 25 mg/mL) and two nano-tubular crystalline structures. Results: In all tested conditions, maximum amount of cefuroxime was obtained within 2 min. For both cefuroxime loading solution concentrations, nano-smooth samples released the least cefuroxime, and the nano-tubular samples released the most, and a six-fold increase in the concentration of the cefuroxime loading increased the amount of cefuroxime quantified by more than seven times, for all tested nano-topographies. However, the nano-tubes’ crystalline structure did not have any influence on the amount of cefuroxime quantified. Conclusion: The results demonstrated that the surface nano-topography and loading solution concentration influence the efficiency of titanium dioxide nanotubes as cefuroxime carriers and need to be optimized for use as novel reservoirs for local delivery of cefuroxime to prevent periprosthetic infections.