Multiple site specific procedures have been proposed to treat obstructive sleep apnea syndrome (OSAS). Midline glossectomy (MLG) is a procedure that directly enlarges the hypopharyngeal airspace using the carbon dioxide laser. The initial experience of 12 patients is presented. Midline glossectomy as the sole procedure was performed on 11 patients who had failed uvulopalatopharyngoplasty (UPPP) and who were felt to have significant hypopharyngeal collapse on physical examination and Müller's maneuver. One patient with primary hypopharyngeal narrowing underwent MLG. Five (42%) were considered responders with Respiratory Disturbance Index (RDI) decreasing from 60.6 per hour to 14.5 per hour. In seven nonresponders, there was no significant change in the RDI (62.6 events per hour to 48.4 events per hour). Cephalometric analysis showed that responders tended to be more retrognathic (sella-nasion-supramentale (S-N-B = 74.4 degrees)) than nonresponders (S-N-B = 79.3 degrees). Responders were significantly less obese (body mass index (BMI = 30.6)) than nonresponders (BMI = 37.9). There were five minor complications including minor bleeding (n = 3), prolonged odynophagia (n = 1), and minor change in taste (n = 1). There were no major complications, and no persistent difficulties with speech or swallowing. These results demonstrate that direct surgical modification of the tongue base and associated structures can significantly impact obstructive apnea. Midline glossectomy or similar procedures may be useful in a subset of patients with OSAS.