Aims Abstract Upper Gastrointestinal bleeding (UGIB) in critically ill patients under mechanical ventilation (MV) is a significant cause of morbidity and mortality. Therefore, it aimed to study the incidence, predictors, and etiology of UGIB in critically ill patients under MV. Patients and Methods Three hundred and sixty critically ill patients were managed by mechanical ventilation. The patients were evaluated by complete clinical examination, APACHE II score, liver and kidney function tests, and abdominal ultrasound. In addition, upper gastrointestinal endoscopy was done for survived patients with UGIB during MV after weaning with a stable clinical condition for at least 48 hours. Results 41 patients (11.4 %) had UGIB; 15 patients (36.6%) survived and death occurred in 26 (63.4%). Upper endoscopy revealed large ulcers > 2 cm in the gastric antrum (n=1), multiple antral ulcers (n=2), large >2cm corporeal gastric ulcers (n=2) [all were Forrest Ib with oozing surface], bleeding small duodenal bulb ulcers < 2cm (n=1) [Forrest Ia with spurting], small ulcers in the lower esophagus with lower end esophagitis (n=2), black esophagus (n=1), ulcer on top of grade III oesophageal varices (n=2), severe portal hypertensive gastropathy (n=3), candida esophagitis and gastritis (n=1). Logistic regression analysis revealed that the independent variables of UGIB were elevated serum creatinine, APACHE II score >14, peak inspiratory pressure ≥ 30cmH2O, and prolonged aPTT. Conclusions Mechanically ventilated patients had a high risk of upper gastrointestinal bleeding, which the postulated parameters can predict for adequate prophylaxis.