Background: Different dosing schedules of CDDP are being used as standard of care for CCRT in LA-SCCHN, but there are no adequately powered trials to directly compare other non-CDDP regimens with CDDP to identify the optimal CCRT regimen. Methods: After obtaining IRB approval, we reviewed medical records from hospital tumor registry for consecutive patients with LA-SCCHN to retrieve data regarding demographics, diagnosis and treatment with definitive CCRT between December 2012 and December 2016. All patients had followed up for at least 24 months after completion of treatment. Results: 155 patients were included in the analysis. They fell into 2 groups: 89 (57.4%) had been administered CDDP and 66 (42.6%) received non-CDDP based regimen. In the latter group, 30 (45.5%) received cetuximab, 30 (45.5%) received carboplatin with paclitaxel, 1 (1.5%) received carboplatin with 5-fluorouracil and 5 (7.6%) received carboplatin alone. The majority of patients in both groups had oropharyngeal involvement, approximately 65%. All patients completed treatment with intensity-modulated radiation therapy. Median age was 57 years in CDDP group and 67 years in non-CDDP group. Patients in both groups were predominantly male, Caucasian, with positive smoking history. 67% patients in CDDP & 59% in non-CDDP group were HPV positive. The 2-year overall survival (OS) from initiation of treatment was 73.9% in CDDP and 62.1% in non-CDDP group (hazard ratio = 1.63, 95% CI 0.92 – 2.87, p = 0.092). Comparing non-CDDP regimens with CDDP, cetuximab appeared to confer better 2 year OS in HPV positive patients (HR 0.63, 95% CI 0.40 – 0.98, p = 0.040). Median time-to-treatment failure was 33 months in CDDP group and 24 months in non CDDP group. Conclusions: In this retrospective comparison, there was no significant difference in the 2 year overall survival in patients with locally advanced squamous cell head and neck cancers being treated with cisplatin based concurrent chemoradiotherapy regimen versus a non-cisplatin based regimen.