Intravenous proton pump inhibitors (IV PPIs) decrease rebleeding following endoscopic hemostasis of bleeding peptic ulcers. Oral PPIs may be equally efficacious and may significantly reduce health care costs. This study aimed to compare outcomes in patients receiving oral versus IV PPI therapy following endoscopic hemostasis in patients with acute nonvariceal upper gastrointestinal bleeding (ANVUGIB). We performed a retrospective review of all patients who received PPI therapy following endoscopic hemostasis for ANVUGIB. The primary outcome was the adverse gastrointestinal event rate. One hundred sixty-two patients met the entry criteria (72 oral PPIs, 90 IV PPIs). The difference in the rate of adverse gastrointestinal events between the two groups was 1% (P = 0.85). Postendoscopic IV PPI use was associated with an odds ratio of 1.01 for developing an adverse outcome versus oral PPIs (95% CI: 0.44-2.33). We conclude that oral PPIs are probably equivalent to IV PPIs for preventing rebleeding in ANVUGIB patients.