We previously synthetized molybdenum oxide (MoO 3 ) nanoparticles (NP) and showed their antibacterial activity against a representative collection of the most relevant bacterial species responsible for hospital-acquired infections, including Staphylococcus aureus. The aim of the present study was to prepare and characterize a novel coating with these MoO 3 NP, confirm its mechanical stability, and investigate its biocidal effect to reduce S. aureus contamination on inanimate surfaces. In addition, the novel MoO 3 NP coating was compared to a silver (Ag) NP coating synthetized by the same procedure. The MoO 3 and Ag NP coatings were characterized in terms of their chemical structure by FT-IR, surface morphology by scanning electron microscopy, and mechanical properties by tensile and adhesion tests. The antimicrobial activity of the coatings was tested by following the loss of viability of S. aureus after 6h, 24h, 48h, and 72h exposure. MoO 3 and Ag coatings exhibited surfaces of comparable morphologies and both presented elastomeric properties (tensile strength of ~420 kPa, Young’s modulus of ~48 kPa, and maximum elongation of ~12%), and excellent (classification of 5B) adhesion to glass, steel and polystyrene surfaces. The two coatings exhibited a good antibacterial activity (R) against S. aureus over time (R MoO3 = 0.2–0.81; R Ag = 0.61–2.37), although the effect of the Ag NP coating was more pronounced, especially at 72h (R MoO3 = 0.81 vs R Ag = 2.37). Noteworthy, contrary to the Ag NP coating, the MoO 3 NP coating was colourless and transparent, avoiding undesired unaesthetic effects. The synthetized coating with NP of MoO 3 , which has low toxicity to humans, capability of biodeg-radation, and rapid excretion, can be applied onto most standard materials and therefore is a promising tool to reduce S. aureus contamination on usual inanimate surfaces found in healthcare and community environments.