Three hundred patients were included in a prospective randomized double-blind trial comparing the efficacy of cefamandole with that of a placebo for prophylaxis of sepsis in operations using Ender or Kuntscher nails, bone plates, or other internal fixation devices. Patients with an open fracture, total joint replacement, or direct operation on the hip were not included in the study. Sixteen patients were excluded because the trial protocol was not followed exactly, so a total of 284 patients participated, 134 of whom were given cefamandole and 150, a placebo. The two groups were similar in terms of mean age, sex ratio, duration of preoperative hospital stay, underlying risk factors, and type of surgical procedure. A superficial wound infection developed in none of the 134 patients who were given cefamandole and in seven of those in the control group (p less than 0.05). Two deep-wound infections developed in the cefamandole-treated group and four, in the control group (p greater than 0.05). Staphylococcus aureus, Staphylococcus epidermidis, and gram-negative bacilli were the most common infecting organisms. The rates of infection-related mortality and abscopal infection were similar in both groups. No adverse side effects of the drug were encountered.