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BACKGROUND: In total knee arthroplasty surgery, a blood conservation program is applied as a normal clinical practice to avoid allogenic transfusions. The objective of this study was to assess the effectiveness of tranexamic acid to reduce transfusions in total knee replacement even when a blood conservation program is applied. STUDY DESIGN AND METHODS: In a double-blind prospective study the patients scheduled for total knee arthroplasty were included in a well-established blood conservation program and then randomly assigned into two groups: In tranexamic acid group, 10 mg per kg ev bolus followed by 1 mg per kg per hour perfusion was administered, while in the control group, saline was given matching the protocol. RESULTS: Ninety-five patients were included (tranexamic acid group, 46; control group, 49). Thirty-three patients (34.7%) underwent preoperative procedures to reduce transfusions: presurgical autologous blood donation (12), recombinant erythropoietin (6), and elementary iron (15); postoperative drain for reinfusion was allocated in all the cases. Total blood loss on the fourth postoperative day was [mean (±SD)] 1744 (±804) mL in controls compared with 1301 (±621) mL in the tranexamic acid group (p < 0.05). Eleven units of blood were transfused (6 patients) in the control group versus one in the tranexamic acid group (p < 0.05). Only 2 patients (4%) in the tranexamic acid group received reinfusion of blood recovered by drains compared with 36 (73%) in the control group (p < 0.0001). No thromboembolic complications were detected. CONCLUSION: Tranexamic acid reduces blood losses and transfusion requirements even when a blood conservation program was used and it questions the usefulness of the postoperative reinfusion drains. [ABSTRACT FROM AUTHOR]