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Introduction: Current guidelines regarding stress ulcer prophylaxis (SUP) recommend prophylaxis in specific and limited situations. Pharmacological SUP, especially with proton pump inhibitors (PPI), may be overused in the medical intensive care unit (MICU). The objective of this study was to evaluate the appropriate use of SUP in adult medical critically ill patients upon admission and discharge. Methods: This was a retrospective, chart review of 100 adult critically ill patients admitted to the MICU from July 2011 to June 2012. Inclusion criteria were: age ≥ 18 years old, admission to the MICU for at least 48 hours, and administration of SUP. Patients diagnosed with a variceal bleed, active peptic ulcer disease, acute gastrointestinal (GI) bleed based on endoscopic exam or chart notation, Zöllinger-Ellison syndrome, or requiring a histamine-2 receptor antagonist (H2RA) for management of an allergic reaction were excluded. Appropriateness of SUP therapy was assessed using the ASHP 1999 SUP guidelines and was evaluated upon admission and discharge, respectively. Descriptive statistics were used to characterize hospital SUP practices and examine the frequency of patients receiving SUP appropriately upon admission to the MICU and at discharge from the MICU. Results: Out of one hundred patients that were enrolled, 86 (95.6%) patients received SUP appropriately. Ninety percent of patients were mechanically ventilated, which was the primary indication for SUP. There were 69 patients (69%) transferred from the MICU to a lower level of care. Of those patients, prescribers discontinued SUP therapy appropriately for only 14 patients. Of the 55 remaining patients who received a SUP agent, 48 (87.3%) received it appropriately based on current recommendations supported by 1999 ASHP guidelines on SUP and primary literature. An additional finding was that of 53 patients who received a PPI, 27 (50.9%) did not meet hospital criteria for receiving a PPI as first-line therapy. Conclusions: A majority of patients received SUP appropriately on admission and discharge from the MICU. However, over half of the patients who received PPI therapy did not meet hospital criteria for receiving a PPI first line. This occurred despite having a team of healthcare professionals caring for the patient which is concerning. The collected data suggest that our hospital may be overprescribing PPIs for patients who could have received H2RAs instead. Based on these findings, further education to the clinicians will be provided.