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Plasma transfusions are given to patients with coagulopathy, either prophylactically, before an invasive procedure; or therapeutically, in the presence of active bleeding; and as an exchange fluid in therapeutic plasma exchange for disorders such as thrombotic thrombocytopenic purpura. There is consensus that many prophylactic plasma transfusions are non-efficacious, and the misdiagnosis of thrombotic thrombocytopenic purpura results in unnecessary therapeutic plasma exchange.Beginning in 2001, programs to reduce plasma transfusion in the three major teaching hospitals in Rhode Island were initiated. The programs evolved through the establishment of guidelines, education for key prescribers of plasma, screening of plasma prescriptions, and engagement of individual prescribing physicians for out-of-guidelines prescriptions with modification or cancellation. Establishment of an in-house ADAMTS13 (ADAM metallopeptidase with thrombospondin type 1, motif 13) assay in 2013 was used to prevent therapeutic plasma exchange in patients with non-thrombotic thrombocytopenic purpura microangiopathy. Transfusion service data were gathered at the hospital level regarding blood component use, hospital data for discharges, inpatient mortality, and mean case-mix index, and, at the state level, for units of plasma shipped from the community blood center to in-state hospitals.Between 2006 and 2016, a reduction in plasma use from 11,805 to 2677 units (a 77% decrease) was observed in the three hospitals and was mirrored in the state as a whole. This decline was not associated with any increase in red blood cell transfusion. Inpatient mortality either declined or was unchanged.An active program focused on education and interdiction can achieve a large decrease in plasma transfusions without evidence of patient harm.