BACKGROUND.: Our aim was to determine feasibility and efficacy of a hybrid radiotherapy schedule in locally advanced head and neck cancer. METHODS.: Seventy-three patients with locally advanced head and neck cancer were irradiated according to a hybrid accelerated schedule consisting of 20 fractions of 2 Gy (once daily), followed by 20 fractions of 1.6 Gy (twice daily), to a total dose of 72 Gy. RESULTS.: Locoregional control was 55% after 2 years. Overall survival was 59%, disease-specific survival was 63%, and disease-free survival was 46%. Acute toxicity was prospectively scored in all 73 patients: the most frequent toxicities were mucositis (50.7%, grade 3), dysphagia (47.9%, grade 3), and dermatitis (34.5%, grade 3). All patients were treated to full dose, without treatment interruption. CONCLUSION.: With this regimen, acceptable locoregional control and survival rates are achieved. Toxicity was well manageable, suggesting that a combination of this schedule with concomitant chemotherapy is possible and could lead to further improvement in the treatment of locally advanced head and neck cancer. (c) 2007 Wiley Periodicals, Inc. Head Neck, 2007.