OBJECTIVES: To assess the feasibility and safety of performing robot-assisted resections of head and neck tumors, and to predict which variables lead to successful robot-assisted resection and better functional outcome. DESIGN: Prospective nonrandomized clinical trial. SETTING: Academic tertiary referral center. PATIENTS: Thirty-six patients with oral cavity, oropharyngeal, hypopharyngeal, or laryngeal tumors. INTERVENTION: Robot-assisted resection of indicated tumors. MAIN OUTCOME MEASURES: Ability to perform robot-assisted resection, final pathologic margin status, ability to extubate postoperatively, need for tracheotomy tube, and need for gastrostomy tube. Any clinically significant complications were recorded. RESULTS: Thirty-six patients participated in the study. Eight patients had previously been treated for head and neck cancer. Twenty-nine patients (81%) underwent successful robotic resection. Negative margins were obtained in all 29 patients. Twenty-one of 29 patients were safely extubated prior to leaving the operating room. One patient required short-term tracheotomy tube placement. A total of 9 patients were gastrostomy tube dependent (2 preoperatively, 7 postoperatively). Factors associated with successful robotic resection were lower T classification (P = .01) and edentulism (P = .07). Factors associated with gastrostomy tube dependence were advanced age (P = .02), tumor location in the larynx (P < .001), higher T classification (P = .02), and lower preoperative M. D. Anderson Dysphagia Inventory score (P = .04). CONCLUSIONS: Robot-assisted surgery is feasible and safe for the resection of select head and neck tumors. This clinical series demonstrates that robotic surgery can be utilized successfully in patients with T1 to T4 lesions located in the oral cavity, oropharynx, hypopharynx, and larynx with good preservation of swallow function.