Background: Q3w CT is standard RT potentiation for HNSCC but its toxicity requires to look for new treatment’s modalities. The aim was to explore if q1w CT could be a safe and effective alternative. Methods: Patients (pts) treated by chemoradiation (CT-RT) for a HNSCC were retrospectively included. Study population was first described. Then overall (OS) and progression-free survival since the RT onset were performed. Survival distributions were estimated by Kaplan-Meier method and compared between CT groups using the Log-Rank test. Prognostic effect of CT group was explored using Cox model. Results: 266 pts treated between January 2004 and December 2008 were included: 170 and 96 pts respectively received q1w and q3w CT. At diagnosis, 46% had oropharynx lesions, 20% larynx, 17% hypopharynx and 14% oral cavity. 70% pts experienced surgery, 39% CT induction and a median dose of radiation of 64 Gy without any significant difference between CT groups. However, median age at diagnosis was significantly different between q1w and q3w CT (58 vs 54, p<0.001) as well as alcohol consumption (79% vs 68, p=0.047), stage at diagnosis (30%-60% stage III-IV vs 13% -80%, p=0.003), IMRT use (4% vs 13%, p=0.011) and median weight before RT (66 kg vs71kg, p=0.014). Q3w CT was more toxic than q1w in terms of weight loss (87% vs 75%, p=0.012), renal failure (50% vs 35%, p=0.022), worse CT plan completion (42% vs 66%, p<0.001). Moreover, grade 3/4 toxicities, such as mucositis (34% vs 13%, p<0.001) and dermatitis (7% vs 1%, p=0.012), were more frequent. More pts needed parenteral nutrition (10% vs 2%, p=0.008), analgesics (91% vs 70%, p<0.001), secondary hospitalization (31% vs 8%, p<0.001), RT interruption >= 3 days (8% vs 2%, p=0.037) and had long-term toxicities (24% vs 12%, p=0.014). With a median follow-up of 42 months 95% CI [36.8-48.8], a trend in favour of q3w CT was found:2-years OS of 83% (95% CI [73-90]) vs 74% (95% CI [66-80]), p=0.089. However, after adjustment on prognostic factors CT group was not significantly associated with OS nor with PFS. Conclusions: Q1w RT-CT is safer than q3w and may be as efficient. Follow-up data will be updated to reinforce efficacy results.