Background: The study aimed to evaluate Hyperfractionated, Accelerated Radiotherapy (HART) with nimorazole for patients with head and neck squamous cell carcinoma (HNSCC) using loco-regional failure (LRF), overall survival (OS), early and late morbidity as endpoints. Material and methods: From February 2007 to January 2018, 295 patients with unresected HNSCC, T1-T4, N0-N3, M0, were treated with HART prescribed as 76 Gy in 56 fractions (fx), 10 fx weekly. IMRT was used in >90% of patients. No chemotherapy was given. Patients were prospectively registered in the DAHANCA database. Results: The median age was 64 years, 75% of patients were males. Primary sites were larynx (25%), pharynx (64%) and oral cavity (11%). In total, 59% were stage III-IV (UICC 2002). Of the 150 oropharyngeal cancer (OPC) patients, 42% were p16+. The proportion of patients receiving HART as planned was 97%. The median follow-up time was 66 months. Three-year actuarial LRF was 19% and OS was 66%. LRF was significantly higher for stage III-IV patients compared to stage I-II (25% vs. 11%, HR 2.12 [1.21-3.74]). The site-specific LRF rates were: for larynx 22% [12-32], hypopharynx 30% [16-45], non-p16+ oropharynx 15% [8-23], p16+ oropharynx 7% [1-13] and oral cavity 35% [18-53]. During therapy, 51% reported severe dysphagia and 60% required feeding tubes. The peak incidence of late, severe dysphagia and xerostomia was 21% and 9%, respectively. A comparison to historical data from previous DAHANCA trials showed that tumor control and morbidity are comparable to treatment with acceleration and/or chemo-radiation. Conclusions: HART represents an attractive approach for patients with HNSCC where treatment intensification is indicated.