The frequency of surgical site infections (SSIs) after clean neck surgery is low and antibiotic prophylaxis is not recommended. This retrospective study investigated the effect of perioperative prophylactic antimicrobial therapy on the development of infections. A total of 807 consecutive patients undergoing clean neck surgery were included in the study. Antimicrobial prophylaxis with intravenous cefuroxime was administered in 518 cases. Although patients who received prophylaxis had a lower rate of SSIs than those who did not receive antibiotics, this was not statistically significant (0.4% vs 1.4% respectively, p=0.19). Older age was the only variable associated with the development of SSIs (p=0.014).