Two well-controlled trials were carried out to investigate the effectiveness of intravenous proton pump inhibitors (PPIs) to reduce peptic ulcer rebleeding after successful hemostasis. The results demonstrated that the PPI reduced the rate of rebleeding significantly. The recent availability of the first intravenous PPI formulation in the United States, intravenous pantoprazole, represents an alternative to intravenous histamine-2 receptor antagonists. The results of 16 randomized, controlled trials involving a total of >3,800 patients (1,892 receiving PPIs and 1,911 controls) suggest that bolus administration plus continuous infusion of PPIs is a more effective pharmacotherapy than bolus infusion alone in decreasing both rebleeding and the need for surgery. Optimal effect is achieved with an intravenous 80-mg bolus, followed by continuous infusion of 8 mg/hr for 3 days, after which therapy may be continued with an oral PPI. Intermittent bolus administration yielded a minimal benefit. A difference in mortality rates has not yet been demonstrated.