Despite many years of published medical society guidelines for red blood cell (RBC) transfusion therapy, along with clinical trials that provide Level 1 evidence that restrictive transfusion practices can be used safely and are equivalent to transfusions given more liberally, annualized blood transfusion activity did not begin to decline in the United States until 2010. Adoption of electronic medical records has subsequently allowed implementation of clinical decision support (CDS): best practice alerts that can be initiated to improve the use of blood components. We describe our own institutional experience using a targeted CDS to promote restrictive blood transfusion practice and to improve RBC use. A 42% reduction in RBC transfusions was demonstrated at our institution from a baseline in 2008 through 2015, and the rate remained stable through 2018. Although the data cannot be used to infer causality, this decreased RBC use was accompanied by improved clinical outcomes.