A total of 41 patients were randomly allocated to receive either cefotetan (total dose, 20 g) or clindamycin (total dose, 12 g) plus amikacin (total dose, 5 g) as perioperative antimicrobial prophylaxis for major head and neck surgery. The two groups were similar in age, male to female ratio, stage of cancer, and the various types of surgery. No patient received radiotherapy or chemotherapy before surgery. The wound infection rate was 4% in the group of patients receiving cefotetan and 0% in the group receiving clindamycin plus amikacin. No major side effects were observed in either group. On the basis of this study a five-day perioperative course with cefotetan may be considered effective antimicrobial prophylaxis in patients undergoing major head and neck oncologic surgery.