Two-hundred and fifty-two patients were included in a prospective, randomized, double-blind trial comparing the efficacy of flucloxacillin with that of cefazolin for clean orthopedic surgery. The preventive antibiotic regimen consisted of three 1-g injections perioperatively. There were 126 patients in each group, and the follow-up period was at least 6 months. Two deep (1.6%) and five superficial (4.0%) infections occurred in the flucloxacillin group. Three deep (2.4%) and five superficial (4.0%) infections developed in the cefazolin group.