Background: Locally advanced head neck squamous cell carcinomas (LAHNSCCs) are treated either with surgery followed by radiation (RT) alone, surgery followed by concurrent chemoradiation (CTRT) or definitive CTRT. Patients receiving RT need to have an optimal hemoglobin (Hb) level, however there is limited data on what is an optimal pre-treatment Hb level required during RT/CTRT in these patients. Hence we performed this analysis. Methods: This data is a pooled analysis of 3 major randomized studies (RCT) performed in the field of chemoradiation over the last decade. These include, a RCT comparing weekly versus (vs) 3 weekly cisplatin in LAHNSCC‘s, weekly cisplatin vs weekly cisplatin plus nimotuzumab in the definitive setting in LAHNSCC‘s and in cisplatin ineligible patients, a comparison of radiation vs docetaxel plus radiation. The baseline demographics, Hb levels, and outcomes were collected and used for analysis. To ensure unanimity, anemia was defined as < 12g/dL in both males and females. Univariate (UVA) and multivariate analysis (MVA) evaluated the factors affecting anemia. The impact of anemia on locoregional control (LRC), disease free survival (DFS) and overall survival (OS) was studied. Kaplan meier analysis was used for estimation of time to event parameters and log rank test was used for comparison. Cox proportional hazards model was used to test the importance of anemia in presence of other important parameters like age, gender, T and N stage, concurrent chemotherapy including its pattern (weekly vs 3 weekly) and site of disease. Results: We studied 1192 patients. Anemia of any grade was seen in 417 patients (35.0%), with the median Hb levels of the entire cohort being 12.8g/dL (IQR 11.6-13.9). Grade 3 or higher anemia (Hb < / = 8g/dL) was seen in only 2 patients (0.2%). Female gender, oral cavity disease, patients with stage IV disease and those receiving adjuvant CTRT significantly impacted anaemia on UVA (p = 0.000 for all). MVA confirmed advancing age (p = 0.001), female gender (p = 0.000), patients with stage III and IV disease (p = 0.009) and those treated with adjuvant CTRT (p = 0.011) to significantly impact anemia. The LRC in patients with or without anaemia was 12.9 months (95%CI 7.8-18.0) and 23.5 months (95%CI 17.8-29.2) respectively (p = 0.000). Similarly the DFS and OS in anemic and non anemic patients were 9.6months (95%CI 6.0-13.2) vs 18.5months (95%CI 12.4-24.7, p = 0.022) and 21.5months (95%CI 16.3-26.8) vs 39.9months (95%CI 31.0-48.9, p = 0.000) respectively. Conclusions: Pre-treatment anemia in LAHNSCC‘s leads to a decrement in treatment outcomes (LRC, DFS and OS) and is an independent prognostic factor.