Objective: To report 2-year survival outcomes for head and neck squamous cell carcinoma using transoral robotic-assisted resection. Design: Prospective case study. Setting: Two tertiary care centers. Patients: Eighty-nine patients from 2 tertiary care centers (University of Alabama at Birmingham and the Mayo Clinic in Rochester, Minnesota) with head and neck squamous cell carcinoma of all stages and subsites, who underwent transoral robotic-assisted resection between March 2007 and December 2008, with a median follow-up time of 26 months. Main Outcome Measures: Disease-free survival, cancer recurrence, and gastrostomy tube dependence Results: Seventy-one patients had T1 (n=29) or T2 (n=42) tumors while 18 patients had T3 (n=8) or T4 (n=10) tumors. There were 24 patients with overall stage I or II disease and 65 with stage III or IV disease. At the time of the last follow-up visit (median, 26 months), there had been a total of 11 patients with recurrent cancer: 3 with local; 7, regional (2 of whom also had distant metastases); and 1, distant. Seven patients were treated for recurrent disease. Eighty-two patients had no evidence of disease, 1 patient died of the disease, 2 died of other disease, and 4 were alive with disease at the last follow-up visit. Results of Kaplan-Meier survival analysis showed that the 2-year recurrence-free survival rate for the cohort was 86.5%. None of the patients were gastrostomy tube dependent at the last follow-up visit. Conclusion: The 2-year functional and oncologic results justify the continued treatment of select patients with head and neck squamous cell carcinoma with roboticassisted surgical resection. ©2010 American Medical Association. All rights reserved.