To evaluate feasibility, functional outcome, and disease control of endoscopic surgery and irradiation in patients with squamous cell carcinoma of the supraglottic larynx. Prospective, single-arm, phase 2 multi-institutional trial. Southwest Oncology Group trial S9709. Thirty-four patients diagnosed as having stage I, stage II, or selected stage III (T1-2N1M0) supraglottic laryngeal carcinoma enrolled from September 15, 1997, to December 1, 2001. Transoral supraglottic laryngectomy by carbon dioxide laser followed by planned postoperative radiotherapy. Three-year progression-free survival, proportion of patients requiring tracheostomy as a result of surgery, and time to adequate oral intake. All 34 patients underwent surgery without major protocol deviation. Thirty-two patients (94%) completed planned postoperative radiotherapy without major deviation. At the time of analysis, only 1 patient (3%) had documented local disease recurrence at the primary disease site and required salvage total laryngectomy, and 2 patients (6%) had documented regional recurrence and required salvage neck dissection. Estimated 3-year progression-free survival and overall survival were 79% and 88%, respectively. No subjects required tracheostomy as a direct consequence of endoscopic resection. Patients who required tracheostomy before endoscopic resection due to either obstructive tumor bulk or unfavorable anatomy that precluded safe intubation (4 patients [12%]) were all decannulated in the early postoperative period (