BACKGROUND: Patients with head and neck cancer (HNC) bear a significant load, due to both disease-related symptoms and to toxicities associated with treatments. Evaluating quality of life (QoL) is crucial to gauge the physical and psychological impact on these patients. Our primary aim was to assess whether QoL has been incorporated as an endpoint in phase II and III clinical trials for HNC patients in the last 15 years. MATERIAL AND METHODS: We investigated publications from 11 major journals to identify randomized and non-randomized phase II and phase III clinical trials assessing locoregional and systemic treatments as either single or multimodal strategies, published from 2008 to March 2023 in patients with HNC. RESULTS: We screened 2045 studies and we selected 158 articles that met the eligibility criteria including a total of 31.734 patients. Globally, QoL was the primary end point in 2 publications (1 %), secondary in 38 (24 %), and exploratory in 7 (4 %). The quota of primary publications with QoL among endpoints increased over time: 14 (17 %) publications between 2008 and 2015 and 33 (42 %) between 2016 and 2023. Notably, in phase III trials, QoL was included among endpoints in 30 (49 %) publications, whereas in phase II studies, QoL was present in 17 (17 %). CONCLUSIONS: In HNC, the assessment of QoL as an endpoint in clinical trials is still missing, even in phase III trials. Efforts should be focused on the adoption of Patient-Reported Outcomes (PROs) in trials to improve the definition of treatment value in this vulnerable population.