Background: Neo-adjuvant chemotherapy (NACT) followed by response assessment is the standard treatment algorithm for locally advanced oral cavity squamous cell carcinomas (OCSCC) in the Indian subcontinent. The 3-drug NACT regimen (Docetaxel-Cisplatin-5-FU) has shown improvement in progression free survival (PFS) and overall survival (OS) over 2-drug regimen (Docetaxel-Cisplatin) in a phase-3 randomised study. We have analysed the 10-year outcomes with this treatment algorithm. Methods: This was an institutional review board approved retrospective analysis of a prospectively collected dataset of borderline resectable OCSCC patients who received NACT. Adults with an eastern co-operative oncology group (ECOG) performance status (PS) 0-2 deemed technically unresectable in a multi-disciplinary clinic were included. All patients received 2-3 cycles of 3-weekly NACT. Patients with good general condition (GC) who became resectable underwent surgery followed by appropriate adjuvant therapy. Patients who were unresectable received definitive chemoradiation (CTRT), palliative chemotherapy, radiotherapy or best supportive care based on GC. The OS was calculated from date of diagnosis to date of death. Kaplan-Meier method was used for estimation of 10-year OS and impact of different regimens on OS was calculated using the log-rank method. Results: A total of 3266 patients were analysed, of which 2857 (87.5%) were males. The median age was 46 years (IQR: 39 - 54). The most common subsites were buccal mucosa (54.7%), tongue (30.4%) and alveolus (7.9%). Patients presented with either stage IVA (51.3%) or IVB (48.7%). The major indications for NACT were edema up to zygoma (42.2%), involvement of hyoid (22.6%), and high infra-temporal fossa (11.5%). The most common NACT was Docetaxel-Cisplatin (50.2%) followed by Docetaxel-Cisplatin-5-Fluorouracil (29.0%) and Paclitaxel-Carboplatin (13.3%). Planned number of NACT cycles could not be completed by 361 (11.1%) patients. Of 3266 patients, 929 (28.4%) underwent surgery followed by adjuvant CTRT (26.7%) or adjuvant RT (1.3%); 13.1% underwent definitive CTRT, 35.8% received palliative chemotherapy, while 11.7% defaulted for definitive treatment. Pathological complete response was seen in 76 (8.2%) patients, while 871 (93.8%) achieved negative margins and 338 (36.4%) had extra-nodal extension. The median OS was 9 months (95% CI: 8.6 – 9.4). NACT with more than 2-drugs had an OS of 13.2 months (95% CI: 12 – 14.4) vs 7.5 months (95% CI: 7.1 – 7.97) for 2-drug regimens. The 10-years OS was also higher for more than 2-drugs regimen - 21% (95% CI - 17.4% – 24.9%) vs 5.14% (95% CI: 3.28% - 7.6%) (p = 0.000). 10-years OS of patients who underwent surgery vs those who did not was 22.28% vs 3.98% (p = 0.000). Conclusions: NACT with more than 2-drug regimens had survival benefit over 2-drug regimens in technically unresectable OCSCC.