Background: For 40 years, pharmacologic prevention of stress ulcer-related gastrointestinal (GI) bleeding with acid suppression has been the standard of care for mechanically ventilated critically ill patients. Worldwide, proton pump inhibitors (PPIs) are more commonly used than histamine-2-receptor antagonists. Pantoprazole is the dominant PPI prescribed in the ICU. However, recent observational studies and a recent network meta-analysis suggest that PPIs increase the risk of ventilator-associated pneumonia (VAP) and Clostridium difficile infection (CDI). Further, the incidence of bleeding from stress ulceration appears to be lower than in the past, perhaps related to earlier resuscitation and enteral nutrition. Given the apparent decline in GI bleeding, and concern about infectious complications, a large randomized trial is needed to test the efficacy and safety of withholding PPIs in the ICU. We successfully completed the 91-patient REVISE Pilot Trial in Canada, Australia and Saudi Arabia, demonstrating a high consent rate (77.8%); recruitment rate (2.6 patients/month/center); and protocol adherence (96.8%), thereby establishing the feasibility of a larger trial.