Staphylococci account for approximately 70% of postoperative infections in orthopedic prosthetic surgery, with the leading organism being Staphylococcus epidermidis. Therefore, the antibiotics most widely used for prophylaxis are cefazolin, cefamandole and cefuroxime, by virtue of their excellent activity against these pathogens. However, methicillin-resistant coagulase-positive and -negative staphylococci are increasingly being reported as the causative agents of postoperative infection in clean prosthetic surgery, therefore prompting the use of glycopeptide antibiotics (vancomycin and teicoplanin) in the prophylaxis for total joint replacement, particularly in hospitals in which there is high methicillin-resistance among these pathogens. Furthermore, in total primary knee replacement (TKR) performed with tourniquet application, regional prophylaxis with teicoplanin (i.e. the injection of teicoplanin into a foot vein of the leg to be operated on after occlusion of the systemic circulation by inflating the tourniquet) has been shown to be a safe and valuable prophylactic technique. Apart from providing teicoplanin concentrations in the operative field higher than those achievable by conventional systemic prophylaxis (i.e. by injecting the antibiotic into an arm vein before application of the tourniquet), regional prophylaxis was found in a prospective, controlled, open study on patients undergoing primary monolateral or bilateral TKR to result in a rate of postoperative infection similar to those achievable with conventional prophylactic regimens.