Background: Proton pomp inhibitor drugs are used in the patients presenting gastrointestinal (GI) bleeding as adjuvant to endoscopic treatment. Proton Pomp Inhibitor (PPI) therapy is used via IV or oral route, with significant difference in cost and convenience. The aim of this study was the evaluation of outcomes in PPI therapy via IV or oral rout in high risk patients (i.e. active bleeding, adherent clot and non bleeding visible vessel). Methods: After endoscopic treatment, high risk patients presenting with upper gastrointestinal bleeding were randomly divided into two groups. Group one including 45 patients who received IV pantoprazole (80 mg stat, and 8 mg/h for 48 hours) and group two 48 patients received omeprazole (40 mg bid for 48 hours). Findings: The mean age of pantoprazole group was 45 ± 18 years (45 patients, Male (28)/Female (17) = 1.6) compared to omeprazole group 42 ± 15 years (48 patients Male (30)/Female (18) = 1.7). The two groups were matched for site of ulcer, age, rate of H. pylroi infection and type of bleeding stigmata. There were no differences between two groups in regards to transfusion units, death, surgery and rebleeding. Conclusion: High dose oral omeprazole is as effective as intravenous pantoprazole in high risk GI bleeding patients treated with endoscopic treatment. Key words: Peptic ulcer, omeprazole, proton pomp inhibitor, upper gastrointestinal bleeding.