Orthopaedic infections represent one of the major causes of implant failure. Systemic treatment is limited due to dosing, side-effects, patient compliance, treatment length and resistant bacteria. The choice of antibiotic incorporation method has been the subject of many investigations and, nowadays, various vehicles for local drug delivery have been studied. In this work, a novel ciprofloxacin loaded chitosan nanoparticles coating system onto titanium surface has been developed and characterized. The antibiotic release capability of this system and its ability to inhibit the in vitro growth of two of the most common pathogens causing orthopaedic implant-related infections, Staphylococcus aureus and Pseudomonas aeruginosa, have been evaluated. Preliminary biocompatibility data arising from MG63 osteoblast-like cells seeding on the ciprofloxacin-loaded systems have also been discussed. The investigated system represents a promising candidate in view of the development of new antibiotic carriers in situ for preventing titanium implant-associated infections.