Background: Managing advanced head and neck squamous cell carcinoma is challenging with a limited outcome, especially in stage IVA disease. However, altered fractionation proved to be a promising alternative to standard radiotherapy. Objectives: This study aimed to explore the effect of concomitant chemotherapy with accelerated fractionation on the disease outcomes. Material and methods: Forty-seven patients were enrolled in this trial. A phase 2 trial with two arms was conducted between Jan 2018 and March 2021. The experimental arm used accelerated fractionation 70 Gy given on 35, six fractions per week. The control arm used a standard fractionation protocol of 70 Gy on 35 fractions, five fractions per week. Chemotherapy using platinum salts was given in both arms. Results: At the end of this study, 44.7% of patients had local-regional relapses, with a one-year loco-regional failure of 40.9%. There was a near significant difference in the one-year loco-regional failure rate between the accelerated and standard fractionation arms (25% versus 54.2%, respectively, p = 0.069). The same near-significant difference was also seen in the cumulative probability of loco-regional failure (28.6% versus 57.7%, respectively, P= 0.076). The rates of grade 3 and 4 acute and late toxicities were comparable in both arms. Conclusion: Accelerated fractionation with concomitant chemotherapy did not improve loco-regional control. However, there was a trend toward improvement. Further evaluation by a large phase 3 trial is mandatory to confirm the results.