A randomized study was carried out to determine the effect of oxygen (3 liters/min) via a novel oxygenating mouthguard (Oxyguard) on arterial oxygenation in 242 intravenously sedated patients undergoing gastroscopy. In another group of 21 patients, a randomized crossover study of arterial oxygen saturation using either the standard mouthguard or the oxygenating mouthguard (3 liters/min) was conducted. Significant O2 desaturation (pulse oximeter reading less than 90%) occurred in 25% of patients on room air but only 3% of those on oxygen (p less than 0.001). Severe desaturation (reading less than 85%) occurred in 5% of patients on room air but was prevented by the oxygenating mouthguard. Minimum oxygen saturation levels were significantly higher in patients on oxygen (90.5 +/- 0.3%) than on air (86.5 +/- 0.5%; p less than 0.001). In the crossover group, O2 saturation was uniformly higher in the recordings of all patients using the oxygenating mouthguard. In conclusion, administration of oxygen via the oxygenating mouthguard alleviates hypoxemia during gastroscopy and prevents severe oxygen desaturation. However, hypoxemia may occur even during use of supplemental oxygen. Hence, monitoring of arterial oxygenation is recommended.