The aim of the present investigation is to evaluate the outcome after induction chemotherapy and concurrent multi-drug chemoradiotherapy (IC/CCRT) with or without post-chemoradiation neck dissection in medically fit elderly patients with loco-regionally advanced head and neck squamous cell carcinoma (HNSCC). Retrospective study including 44 elderly patients (median age 71 years; range 66-77 years) with previously untreated, inoperable, histologically proven non-metastatic stage III or IV HNSCC. Following one cycle of IC, two cycles of cis-platinum and 5-fluorouracil CCRT with conventional fractionated radiotherapy up to a dose of 66-70 Gy were administrated. A neck dissection was recommended for patients with node metastasis larger than 3 cm regardless of the response to therapy and for patients who had suspected persistent neck disease 8-12 weeks after completing treatment. Salvage surgery was considered for histologically proven persistent or recurrent tumor in the primary site. Time-to-event data were described using Kaplan-Meier actuarial curves. Overall, 37 patients (84.1%) completed the planned treatment. There were no cases of treatment-related deaths. Twenty-nine patients (65.9%) developed severe toxicities with grade 4 toxicity accounting for 22.7%. The median follow-up time in survivors was 41 months. Three-year overall survival, progression-free survival, and functional progression-free survival estimates were 70.9, 67.0, and 57.3%, respectively. In selected medically fit elderly patients with loco-regionally advanced HNSCC, cis-platinum-based chemoradiotherapy can be successfully applied, with moderate adverse events, in attempt to preserve a functional upper aerodigestive tract.