Radiotherapy causes both epithelial and endothelial damage acutely with the subsequent development of interstitial and perivascular fibrosis. These effects may lead to decreased blood flow, delayed wound healing, and a delay in achieving normal wound tensile strength. In a retrospective study of wound infections that developed in 23 of 354 patients (6%) accrued in a series of prospective, randomized antibiotic trials, the incidence of wound infection in patients receiving prior radiotherapy (7.6%) was not statistically different from the incidence of wound infection observed in patients who had had no prior radiotherapy (6.3%). Wound infection that developed in patients after radiotherapy tended to be associated with increased hospitalization, an increased rate of fistulization, and more frequently required secondary surgical repair. It is concluded that major head and neck procedures can be accomplished without an absolute increase in the incidence of wound infection. However, when postoperative complications occur, it may result in a significant increase in morbidity.