Objectives: Glucocorticoids are widely used in association with major surgery of the head and neck to improve postoperative rehabilitation, shorten intensive care unit and hospital stay, and reduce neck swelling. This study aimed to clarify whether peri-and postoperative use of dexamethasone in reconstructive head and neck cancer surgery is associated with any advantages or disadvantages. Materials and methods: This prospective double-blind randomized controlled trial comprised 93 patients. A total dose of 60 mg of dexamethasone was administered to 51 patients over three days peri-and post-operatively. The remaining 42 patients served as controls. The main primary outcome variables were neck swelling, length of intensive care unit and hospital stay, duration of intubation or tracheostomy, and delay to start of possible radiotherapy. Complications were also recorded. Results: No statistical differences emerged between the two groups in any of the main primary outcome variables. However, there were more major complications, especially infections, needing secondary surgery within three weeks of the operation in patients receiving dexamethasone than in control patients (27% vs. 7%, p = 0.012). Conclusions: The use of dexamethasone in oral cancer patients with microvascular reconstruction did not provide a benefit. More major complications, especially infections, occurred in patients receiving dexamethasone. Our data thus do not support the use of peri-and postoperative dexamethasone in oropharyngeal cancer patients undergoing microvascular reconstruction. (C) 2016 Elsevier Ltd. All rights reserved.