The rationale for use of perioperative shortterm prophylactic antibiotics in prevention of postoperative infection in major head and neck surgery was reviewed. Cefazolin and placebo were compared in 50 patients and results showed that short-term perioperative cefazolin was a useful adjunct in reduction of postoperative infection. Findings suggest perioperative antibiotics may be safely and effectively used to reduce postoperative morbidity from infection after surgical procedures in volving skin and mucosa of the upper aerodigestive tract.