ObjectiveTo research on the advances of stress ulcer drug prophylaxis. MethodsGuidelines for stress ulcer prophylaxis in and out of China were searched and analyzed. Risk factors for stress ulcer, recommended prevention drugs and safety of medicines were summarized. ResultsThe risk factors for stress ulcer included mechanical ventilation, coagulopathy, severe sepsis, multiple organ failure, shock, severe head injury, burns, major trauma, older than 65 and drug use. The recommended prevention drugs included proton pump inhibitors, H2-receptor antagonist and misoprostol, which played a role in the reduction of bleeding in intensive care units. However, recommended drugs had little function in the reduction of bleeding in general patients outside the intensive care units, which was even not recommended or supported in the clinical literature. Related adverse effects of these drugs also needed careful consideration. ConclusionExistence of risk factors for stress ulcer does not necessarily indicate the use of preventive drugs. Drug prophylaxis is used only for critically ill patients. This view summarized by the author provides a reference for physicians and pharmacists.