This study was designed to evaluate the effects of a prophylactic antibiotic regimen on the incidence of wound infection after clean neck dissections. A prospective series of 57 patients undergoing clean neck dissections with the use of perioperative ampicillin-sulbactam for 24 hours was compared with an historical control group of 51 patients undergoing clean neck dissections with no perioperative antibiotic use. The outcome variable was the incidence of post-operative wound infection. The two groups were similar for factors reported to influence the rate of post-operative wound infection. Wound infection occurred in one patient (1.7 per cent) in the study group and in seven patients (13.3 per cent) in the control group, the difference was statistically significant (p = 0.02). These data suggest that the use of a perioperative antibiotic for 24 hours in patients undergoing clean neck dissection results in significant reduction in the incidence of post-operative wound infection.