Infections and their consequences are a considerable problem in orthopaedic surgery. Despite intravenous prophylactic antibiotic administration, infection rates can reach in some occasions more than 1%. Indeed, the concentration in bone tissues is very low with the majority of antibiotics. Because high local dose can be obtained, the local release of gentamicin from acrylic bone cements has been shown to be efficient in preventing infections. However, for surgical procedures other than cemented prostheses no other local antibiotic releasing device is clinically available. The purpose of this study was to validate the concept of a gentamicin loaded bone substitute. About 125 mg of gentamicin were introduced into a HAP/TCP bone substitute for prophylactic purpose, to enhance the efficiency of systemic antibiotic treatments. The release rate of gentamicin from the bone substitute was investigated in vitro, in 0.9% sodium chloride solution. The rate appeared to be related to the bone substitute volume. All the gentamicin was released in less than 48 h. This release rate corresponds to the recommendations for the prophylactic use of antibiotics: the duration of the treatment should be less than 48 h, not to select antibiotic-resistant bacterial strains.