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Abnormal bleeding after cardiopulmonary bypass (CPB) is a common complication of cardiac surgery, with important health and economic consequences. Coagulation test–based algorithms may reduce transfusion of non-erythrocyte allogeneic blood in patients with abnormal bleeding.The authors performed a randomized prospective trial comparing allogeneic transfusion practices in 92 adult patients with abnormal bleeding after CPB. Patients with abnormal bleeding were randomized to one of two groups: a control group following individual anesthesiologist’s transfusion practices and a protocol group using a transfusion algorithm guided by coagulation tests.Among 836 eligible patients having all types of elective cardiac surgery requiring CPB, 92 patients developed abnormal bleeding after CPB (incidence, 11%). The transfusion algorithm group received less allogeneic fresh frozen plasma in the operating room after CPB (median, 0 units; range, 0–7 units) than the control group (median, 3 units; range, 0–10 units) (P = 0.0002). The median number of platelet units transfused in the operating room after CPB was 4 (range, 0–12) in the algorithm group compared with 6 (range, 0–18) in the control group (P = 0.0001). Intensive care unit (ICU) mediastinal blood loss was significantly less in the algorithm group. Multivariate analysis demonstrated that transfusion algorithm use resulted in reduced ICU blood loss. The control group also had a significantly greater incidence of surgical reoperation of the mediastinum for bleeding (11.8%vs. 0%;P = 0.032).Use of a coagulation test–based transfusion algorithm in cardiac surgery patients with abnormal bleeding after CPB reduced non-erythrocyte allogeneic transfusions in the operating room and ICU blood loss.