Background The best chemoradiation regimen to treat locally and regionally advanced head and neck squamous cell carcinoma (HNSCC) is yet to be established. Methods We compared overall survival (OS) and adverse events following chemoradiation regimens (high‐dose HDC or low‐dose LDC cisplatin, or carboplatin CB) in HNSCC cases selected from SEER‐Medicare linked database. Results Of the 1335 cases who underwent radiotherapy, 264 received HDC, 259 received LDC, and 353 received CB, concurrently. Compared to chemoradiation with HDC, using LDC or CB, or radiotherapy alone were associated with an increasingly worse OS; hazard ratios were 1.33, p = 0.03; 1.35, p = 0.02; and 2.12, p < 0.001; respectively. There were no differences in the rates of adverse events between the three chemoradiation regimens. Conclusion Chemoradiation regimen using HDC appears to be the best primary treatment for locally and regionally advanced HNSCC. Nonetheless, prospective large studies are warranted to further determine its absolute benefit.