Background: For patients with primary untreated locally advanced head and neck squamous cell carcinoma (PULA-HNSCC), high dose once every 3 weeks cisplatin (HDC; 100 mg/m²) added to curative radiotherapy (RT) prolongs survival, but is associated with severe toxicities. Concurrent chemoradiation (CRT) with low dose weekly cisplatin (LDC; 30-40 mg/m²), carboplatin (C), or RT alone is often substituted for HDC. We estimated and compared overall survival (OS) and acquired toxicities among Medicare beneficiaries treated with CRT using HDC, LDC, C, or RT. Methods: Patients diagnosed from 2004-2011 with PULA-HNSCC (stages III-IVB AJCC 6^th and 7^th editions) of the oropharynx (OPC), hypopharynx (HP), or larynx (L) who received definitive RT or CRT were identified using the linked SEER-Medicare database. An analytic cohort of patients receiving CRT with HDC, LDC, or C was constructed using well-established eligibility criteria. OS was estimated and compared between patients grouped by treatment received utilizing a multivariable stratified propensity scores weighted Cox regression model, including demographic and disease characteristics. Toxicities were compared using exact common odds-ratio and Fisher’s tests. Results: We identified 1,335 patients that received RT: OPC (n = 731), HP (n = 174), or L (n = 430). Out of those, patients were treated with HDC (n = 264), LDC (n = 259), C (n = 353), or RT alone (n = 459). Median OS (years) was 5.61 (95% CI = 4.58-7.69) for HDC, 3.7 (95% CI = 3.1-4.79) for LDC, 3.1 (95% CI = 2.48-3.86) for C, and 1.36 (95% CI = 1.19-1.58) for RT, respectively. OS was significantly greater for HDC than for LDC (HR = 1.35, 95% CI = 1.06-1.72, p= 0.02), C (HR = 1.41, 95% CI = 1.12-1.76, p= 0.003), or RT (HR = 2.1, 95% CI = 1.68-2.61, p= < 0.001). Treatment with HDC compared to LDC was not associated with increased prevalence of dysphagia or neutropenia. HDC was associated with hearing loss when assessed at 9-12 months post-diagnosis (p =0.03). Conclusions: In SEER-Medicare beneficiaries with PULA-HNSCC of the OPC, HP, or L, OS was significantly better for HDC than LDC when accounting for baseline clinical and demographic characteristics and propensity score weights. Toxicities were similar between regimens, except for an increased incidence of the late acute toxicity of hearing loss in HDC. A regimen of HDC improves OS, but needs to be carefully assessed against increased toxicity risk, with hearing loss in particular.