A prospective study was conducted to see whether emergent esophagogastroduodenoscopy (EGD) in patients with active upper gastrointestinal (GI) bleeding is associated with more oxygen desaturation than nonemergent EGD. Emergent EGD was performed in the study patients with active upper GI bleeding. Nonemergent EGD was performed in the control patients. Determination of oxygen saturation (Sao2) was measured by pulse oximeter. A decrease in Sao2 of > 4% was more frequent in the study patients (26%, 13 of 50) than in controls (6%, 3 of 50) (P < .01). During EGD, mean oxygen saturation decreased significantly in both groups of patients. After EGD, mean oxygen saturation did not recover toward the pre-endoscopy insertion level in the study group (P < .01). A linear association was found that oxygen desaturation = 5.46 + 0.15 (status) -0.06 (baseline oxygen saturation). Emergent EGD for active upper GI bleeding in the emergency department tends to be associated with more frequent significant oxygen desaturation than nonemergent EGD. Continuous oxygen supplementation and oxygen saturation monitoring may be used during emergent nonsedated EGD in the emergency department.