Histamine2 (H2)-receptor antagonists are widely prescribed for a variety of acid-mediated gastrointestinal disorders. The objective of the present study was to quantify the frequency of inappropriate H2-receptor antagonist use and its economic impact in patients who were admitted to a critical care bed at our hospital and followed as outpatients for 1 year. Eighty-eight (72%) of 123 patients admitted to the coronary care unit (CCU) or the intensive care unit over a 14-day period received H2-receptor antagonists. Forty-five (51%) of the 88 patients did not have a documented indication for H2-receptor antagonist therapy. Most of the patients without indications were admitted to the CCU for cardiac diagnoses. Thirty-eight patients (43%) were discharged on oral H2-receptor antagonist therapy. Twenty (53%) of the 38 patients had no documented indication for therapy; 17 of these patients continued H2-receptor antagonist therapy for 1 year, whereas the remaining 3 patients received therapy for 1, 2, and 3 months, respectively. The cost of therapy for the 45 patients receiving inappropriate therapy during hospitalization was $5,084.31. Outpatients costs for the 20 patients remaining on inappropriate therapy was $8,619.75. The total cost of inappropriate therapy was $13,704.06. If data collected during this 2-week period were extrapolated to 1 year, the projected annual cost of inappropriate therapy would be $356,305.56. The economic impact of inappropriate H2-receptor antagonist therapy at our institution is great. Programs designed to reduce such inappropriate use must be implemented and evaluated for their ability to decrease the associated costs.