Obstructive sleep apnea syndrome is caused by narrowing of the pharyngeal airway and loss of dilator tone during sleep. In patients with severe apnea surgical correction often requires attention to both the oropharynx and hypopharynx. Tongue reduction surgery has been described for persistent apnea after failure of palatal surgery. We describe our experience with midline glossectomy with epiglottidectomy in 12 patients with a mean age of 48.8 +/- 14.2 years and body mass index of 36.0 +/- 8.8 kg/m2. Response to treatment was defined as a postoperative respiratory disturbance index (RDI) below 20. Three patients (25%) responded to treatment. The mean apnea index decreased from 48.9 to 35.7, RDI decreased from 73.3 to 46.6, and lowest oxygen saturation increased from 65.9 to 77.9%. RDI in responders decreased from 69.7 to 10. Midline glossectomy with epiglottidectomy has variable results, yet is effective in selected patients with hypopharyngeal narrowing related to macroglossia.