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Simple Summary: During radiotherapy, many patients with head and neck cancer (HNC) experience distressing symptoms that might impact their health-related quality of life (HRQoL) and their ability to cope with the treatment. The objective of this study was to analyze the implementation of nurse-led consultation and the potential associations with symptom burden in HNC patients. Our study included 134 patients, of whom 72 received routine care and 62 received nurse-led consultations. The study was conducted at Lausanne University Hospital between 2017 and 2019. A larger proportion of patients in the routine care group reported severe symptoms; however, no relevant differences in main symptom burden over time were observed between the two groups. Nurse-led consultation has not yet been fully implemented and might be further investigated, involving larger populations, a more detailed process evaluation of the implementation, and the evaluation of the long-term impact of the intervention. Background: Head and neck cancer (HNC) patients experience distressing symptoms that can significantly impact their health-related quality of life (HRQoL). We analyzed the implementation of a nurse-led consultation (NLC) and explored potential associations with symptom burden in HNC patients. Methods: We retrospectively analyzed routinely collected data to describe the implementation of the nurse-led interventions and the evolution of the M.D. Anderson Symptom Inventory scores as patient-reported outcome measures (PROMs). Patients who received routine care (n = 72) were compared with patients in the NLC group (n = 62) at a radiation oncology unit between 2017 and 2019. PROMs were measured at T0 (between simulation and the first week of radiotherapy), T1 (week 3–4), and T2 (week 5–6). Results: Screening for nutrition, smoking, oral cavity status, and capacity for swallowing/chewing, but not for pain, was applied in >80% of patients in the NLC group from T0 to T1. Education (16%) and care coordination (7%) were implemented to a lesser extent. Symptom burden increased over time with no significant differences between groups. Conclusions: The nurse-led consultation was not associated with symptom burden over time. A larger implementation study including a detailed process evaluation, larger sample size, and a focus on long-term effects is needed. [ABSTRACT FROM AUTHOR]