Relevance: Most mechanically ventilated patients around the world receive daily stress ulcer prophylaxis, although international variation exists such that some centers do not use any. Many of the RCTs of stress ulcer prophylaxis were conducted 10-30 years ago, several are at moderate or high risk of bias, and cointerventions in those trials do not reflect current ancillary critical care management. Today, infectious complications of PPIs have emerged as potentially more common and serious than upper GI bleeding. The number needed to prophylax to prevent 1 GI bleed and the cost per GI bleed averted may be very high; furthermore, the number needed to harm to cause 1 episode of VAP or CDI may be low. Recent practice guidelines are conflicting. The apparent decline in the incidence of upper GI bleeding, and doubts about the effectiveness and safety of PPIs, demand re- examining universal prophylaxis for possible de-adoption. Aligned with the 'Choosing Wisely' Campaign, REVISE and the companion economic evaluation (E-REVISE) will be incorporated into guidelines to inform global practice.