Oral appliances for the treatment of obstructive sleep apnea (OSA) produce either mandibular or tongue protrusion, and are thought to enlarge the upper airway (UA). We used videoendoscopy to measure UA cross-sectional area (CSA) and shape in the hypopharynx, oropharynx, and velopharynx during various stages of active mandibular and tongue protrusion during wakefulness in 10 patients with OSA and nine control subjects. Measurements were made in the supine position at end-tidal expiration, and were normalized to the CSA in the normal bite position. Airway shape was expressed as the anteroposterior/lateral (AP/L) diameter ratio. There were no differences between OSA patients and controls in the effects of mandibular and tongue protrusion on UA caliber. Both mandibular and tongue protrusion increased CSA in the hypopharynx and oropharynx (p < 0.001), whereas only tongue protrusion increased CSA in the velopharynx (p < 0.001). Tongue protrusion caused a greater increase in oropharyngeal and velopharyngeal CSA than did mandibular protrusion (p < 0.05). Mandibular protrusion caused a greater increase in CSA in the hypopharynx than in the oropharynx or velopharynx (p < 0.05). Obese patients had a larger relative increase in oropharyngeal CSA with mandibular and tongue protrusion than did subjects of normal weight. Tongue protrusion increased the AP/L diameter ratio in the oropharynx and velopharynx (p < 0.001), and mandibular protrusion did so to a lesser extent in the oropharynx (p < 0.01), resulting in a more circular airway shape. We conclude that mandibular and tongue protrusion increase the CSA and alter the shape of the UA during wakefulness.