Since new treatment strategies, such as chemoradiotherapy, have been introduced for head and neck cancer, a higher number of unknown factors may be involved in surgical site infection in clean-contaminated head and neck cancer surgery. The aim of the present study was to clarify the risk factors of surgical site infection in clean-contaminated surgery for head and neck cancer and the prognosis of patients with surgical site infection. Participants were 277 consecutive patients with head and neck cancer who underwent clean-contaminated surgery for primary lesions at the Aichi Cancer Center over a 60-month period. A total of 22 putative risk factors were recorded in each patient and statistically analyzed to elucidate surgical site infection related factors. Surgical site infection was observed in 92 (32.1 %) of 277 cases. Univariate analysis indicated that alcohol consumption, T classification, neck dissection, reconstructive procedure, and chemoradiotherapy were significantly associated with surgical site infection. Multiple logistic regression analysis identified two independent risk factors for surgical site infection: reconstructive surgery (p = 0.04; odds ratio (OR) 1.77) and chemoradiotherapy (p = 0.01; OR 1.93). In spite of surgical site infection, the five-year overall survival rate of patients with surgical site infection was not significantly different from those without surgical site infection. Although surgical site infection did not impact the overall survival of patients with surgical procedures, head and neck surgeons should pay attention to patients with previous chemoradiotherapy as well as to those with a high risk of surgical site infection requiring reconstructive surgery.