Hospital stays constitute the main component of costs of cancer treatment. We conducted a prospective study to identify the determinants of the length of stay (LOS) after head and neck cancer surgery (HNCS). Patients who underwent major HNCS with opening of mucosa and with curative intent were enrolled. Data were collected for patient characteristics, type of tumour, surgical procedures and postoperative outcome. LOS defined as the interval between the day of admission for surgery until hospital discharge or death was determined by the Kaplan-Meier method. Independent determinants of LOS were identified using a Cox model. All 260 patients were included. Median LOS was 26 days (range, 3-178). In the multivariate model, four variables remained associated with increased LOS: American Society of Anaesthesiologist's score equal to 3 (hazard ratio 1.62 [1.23-1.99]), duration of surgical procedure >220 min., (HR=1.37 [1.22-1.56]), SSI (HR=2.09 [2.02-2.54]), occurrence of SSI caused by multi-resistant pathogen (HR=2.92 [2.78-3.77]) and occurrence of PP (HR=2.09 [1.78-2.81]). The present results highlighted the long duration of LOS after head and neck cancer surgery. Two variables (duration of surgical procedure and occurrence of nosocomial infections) were associated with LOS and might be improved by appropriate strategies.