164 Background: Routine diphenhydramine premedication to prevent allergic transfusion reactions is common practice despite lack of evidence. First-generation antihistamines are associated with a number of anticholinergic side effects such as sedation and cognitive impairment that impact patient care and increase cost. Because premedication should be evidence-based and patient-specific, the University of California, San Diego (UCSD) inpatient Bone Marrow Transplant (BMT) service implemented a transfusion premedication protocol, specifically addressing antihistamine use. Methods: To revise the protocol, a committee was formed. The committee reviewed evidence-based practices, challenges, pharmacology, and costs of antihistamines, and developed an inpatient BMT antihistamine premedication protocol that omitted pre-ordered diphenhydramine and offered cetirizine as a first-choice premedication. Antihistamine premedication was encouraged for high risk patients only. A retrospective comparison of antihistamine prophylaxis pre (2010-2011) and post (2011-2012) protocol implementation was completed. The number of antihistamine doses and transfusions was computed by a count from the electronic medical records. Results: Despite a 14% increase in transfusions, the number of BMT inpatient antihistamine premedication orders decreased by 26%. Diphenhydramine use decreased from 85.9% to 34.2%, while cetirizine use increased from 3.3% to 55.9%. Conclusions: The evidence-based, risk-stratified antihistamine premedication protocol decreased the use of diphenhydramine. Limitations include the retrospective design and lack of data comparing reactions in patients who did and did not receive premedication. Our institution plans to expand this study and complete a prospective evaluation of safely and rationally administered transfusion premedication with the goal to evaluate premedication-related toxicity and methods to improve the quality of life in our patients. [Table: see text]