Antimicrobial prophylaxis, to reduce the incidence of postoperative infections, has been a controversial subject. The administration of antibiotics just prior to and up to 3 hours after operation has been demonstrated to be effective in preventing experimental staphylococcal wound infection in animals. However, the use of prophylactic antibiotics in orthopedic surgery has been tested in appropriate clinical trials only in the treatment of fractured hip. In that setting, prophylactic antibiotics were found to be efficacious. Although used extensively in other procedures such as total hip replacement, statistically valid evidence of the efficacy of prophylactic antibiotics has not been produced. Suggestions are offered for the conduct of clinical trials to study this important question.