AbstractClinical questionWhat is the role of gastrointestinal bleeding prophylaxis (stress ulcer prophylaxis) in critically ill patients? This guideline was prompted by the publication of a new large randomised controlled trial.Current practiceGastric acid suppression with proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs) is commonly done to prevent gastrointestinal bleeding in critically ill patients. Existing guidelines vary in their recommendations of which population to treat and which agent to use.RecommendationsThis guideline panel makes a weak recommendation for using gastrointestinal bleeding prophylaxis in critically ill patients at high risk (>4%) of clinically important gastrointestinal bleeding, and a weak recommendation for not using prophylaxis in patients at lower risk of clinically important bleeding (≤4%). The panel identified risk categories based on evidence, with variable certainty regarding risk factors. The panel suggests using a PPI rather than a H2RA (weak recommendation) and recommends against using sucralfate (strong recommendation).How this guideline was createdA guideline panel including patients, clinicians, and methodologists produced these recommendations using standards for trustworthy guidelines and the GRADE approach. The recommendations are based on a linked systematic review and network meta-analysis. A weak recommendation means that both options are reasonable.The evidenceThe linked systematic review and network meta-analysis estimated the benefit and harm of these medications in 12 660 critically ill patients in 72 trials. Both PPIs and H2RAs reduce the risk of clinically important bleeding. The effect is larger in patients at higher bleeding risk (those with a coagulopathy, chronic liver disease, or receiving mechanical ventilation but not enteral nutrition or two or more of mechanical ventilation with enteral nutrition, acute kidney injury, sepsis, and shock) (moderate certainty). PPIs and H2RAs might increase the risk of pneumonia (low certainty). They probably do not have an effect on mortality (moderate certainty), length of hospital stay, or any other important outcomes. PPIs probably reduce the risk of bleeding more than H2RAs (moderate certainty).Understanding the recommendationIn most critically ill patients, the reduction in clinically important gastrointestinal bleeding from gastric acid suppressants is closely balanced with the possibility of pneumonia. Clinicians should consider individual patient values, risk of bleeding, and other factors such as medication availability when deciding whether to use gastrointestinal bleeding prophylaxis. Visual overviews provide the relative and absolute benefits and harms of the options in multilayered evidence summaries and decision aids available on MAGICapp.