Nowadays PPI present cornerstone in the medical therapy of bleeding peptic ulcer. Controlled pantoprazole data in peptic ulcer bleeding are few. To compare the effect of intravenous (iv) pantoprazole (PPI) with iv ranitidine (H2RA) for bleeding peptic ulcers after endoscopic therapy. After endoscopic haemostasis, 122 patients were randomized to PPI 80 mg + 8 mg/h or H2RA 50 mg + 13 mg/h, both for 72 h and to continue with oral equivalent dose of these medicaments. Patients underwent second-look endoscopy on day 3 or earlier, if clinically indicated. The primary endpoint measure was rebleeding before discharge and <14 days of enrollment. Secondary endpoint measures included number of surgeries performed, volume of blood transfusion, mortality rate and hospital stay. All data were statistically analyzed and a value of 0.05 or less was considered to indicate statistical significance. In the group who were treated with PPI, re-bleeding rate was evidenced in 5 patients (8.33%) and in the groups who were treated with H2RA, re-bleeding rate was found in 9 patients (14.5%) with RR 0.27 and CI 0.12-0.60 and P < 0.05. The volume of transfused blood was lower in the group treated with PPI compared to the group treated with H2RA (930 ml vs. 1540 ml and P < 0.05). In this study there was not statistically significant difference in the hospital stay 15.00 vs. 17.80% (9 vs. 11 patients and P> 0.05), the need for surgical intervention 5.00 vs. 6.45% (3 vs. 4 patients and P= 1.00) and the mortality rate 1.66 vs. 3.22% (1 vs. 2 patients and P > 0.05). A high-dose pantoprazole infusion is more effective than a ranitidine infusion for prevention of re-bleeding after endoscopic epinephrine injection in patients with peptic ulcers and active bleeding or non-bleeding visible vessels (P < 0.05). In all bleeding peptic ulcer patients is needed to make the eradication of H. pylori infection with the aim to prevent re-bleeding in long term.