Background: The standard of care for OPSCC includes chemoradiation (CRT) or surgery with adjuvant radiation (RT). However, RT is associated with significant life long morbidity. We assessed the efficacy of a two-drug induction regimen, followed by transoral robotic assisted surgery (TORS) & neck dissection for locally advanced OPSCC. Methods: This is an IRB approved single-arm phase II study for untreated stage III or IVA (AJCC 7^th edition) OPSCC patients (pts) with an ECOG < 2 and GFR >50 cc. Induction chemotherapy consisted of cisplatin 75 mg/m2 and docetaxel 75 mg/m2 every 21 days for 3 cycles. Tumor shrinkage was examined after each cycle. If the primary tumor was ≥ 80% smaller, pts underwent TORS and neck dissection(s). At post-op visits, flexible laryngoscopy, blood tests, and imaging with PET/CT and/or MRI were done. Short and long term toxicity, progression-free survival, overall survival, and quality of life (QOL) were evaluated. Results: Twenty pts were treated, nineteen were male, 17 were Caucasian, and 19 were HPV+. Median age at diagnosis was 57. Tumors involved the tonsil (13 pts) and base of tongue (7 pts). Three pts were stage III, and 17 were stage IVA. Tumor size was reduced by 53.4%, 80% and 90.5% after the 1st, 2^nd and 3^rd induction cycles respectively. Pathologic CR of the primary site occurred in 15 pts and CR among LN neck dissections occurred in 13 pts. Four pts were given dose-reduced chemo and one pt was changed to carboplatin per protocol because of renal dysfunction. Pre vs post tx QOL scores did not change. At a mean follow-up of 21 months (range 7.6 to 32.1), 18 pts are alive and NED. Three pts recurred a mean of 2.2 months after surgery, and were treated with salvage CRT. Two pts died of metastatic disease, the third is alive and well. All 3 pts had positive LN (9 LN, 3 LN and 1 LN) at surgery. Conclusions: Cisplatin + docetaxel followed by TORS & neck resections appears to be an effective model for the definitive treatment for OPSCC, while avoiding the adverse effects of RT. Clinical trial information: NCT02760667