Background: The combination of endoscopic therapy and intravenous proton pump inhibitor (PPI) in treating peptic ulcer bleeding (PUB) has been shown to reduce re-bleeding rate. PUB patients with uremia are prone to re-bleed. Aim: To compare the efficacy of endoscopic therapy and subsequent intravenous PPI in high-risk PUB patients with or without uremia. Methods: Uremic and non-uremic patients having high-risk (adherent clot, NBVV and oozing) PUB were enrolled. We excluded cases with COPD, CAD, liver cirrhosis, bleeding tendency, pregnancy, gastric cancer, prior gastric surgery, and recent use of anti-secretory agents within one week. All patients received a successful endoscopic therapy with epinephrine injection (1: 10000, 5-15 ml) plus intravenous omeprazole, 40mg bolus followed by 40mg infusion every 12 hrs for 3 days. The primary outcomes including re-bleeding, need of surgery, all-cause mortality and secondary outcomes including units of blood transfusion, hospital stay, and complication were analyzed. The study was approved by the ethical committee of Ton-Yen General Hospital, Hsin-Chu, Taiwan. Results: From September 1999 to December 2006, a total of 64 patients (uremia: 31 and non-uremia: 33) were included. Their demographic data such as age, gender, personal and past medical history, and presenting symptoms were similar in both groups. The endoscopic features including gastric content, ulcer size, stigmata of recent hemorrhage, and the amount of injected epinephrine were comparable between both groups. The uremic group had more re-bleeding episodes (8/31 vs 1/33, p=0.009, OR(95%CI): 11.31(1.30-95.25)), all-cause mortality (4/31 vs 0/33, p=0.033, OR(95%CI): 1.148 (1.003-1.315)), units if blood transfusion after endoscopic therapy (mean (SD): 4.55(3.39) vs 1.91(1.72), p<0.001), hospital stay (day, median(range): 5 (2-48) vs 3(2-7), p<0.001), and complications during hospitalization (9/31 vs 0/33, p=0.001, OR(95%CI): 1.409 (1.125-1.176)). The need of surgery was not significantly different in both groups (1/31 vs. 0/33, p=0.298). Conclusion: Endoscopic therapy with epinephrine injection plus IV PPI has a limited value in uremic patients with high-risk PUB patients.