This study is a large-scale comparative effectiveness study which will establish the safety and efficacy of using proton pump inhibitors versus histamine-2 receptor blockers as the routine strategy for stress ulcer prophylaxis in mechanically ventilated intensive care unit (ICU) patients. The study will use the innovative approach of collecting outcome data from existing databases. This will allow us to complete a high quality, prospective interventional trial in 25,360 participants in 40 ICUs for very low cost. This study will be the first that is adequately powered to determine whether or not the choice of stress ulcer prophylaxis in the ICU affects the risk of developing important complications such as bleeding from stomach ulcers and hospital acquired infections. Currently stress ulcer prophylaxis with either proton pump inhibitors or histamine-2 receptor blockers is administered to more than two million patients a year in developed countries alone.