BACKGROUND: Tranexamic acid (TXA) is efficiently used to control blood loss during total knee arthroplasty (TKA). The role of intraarticular epinephrine needs further clarification. Limited data exist, concerning the combined use of intravenous and intraarticular TXA plus epinephrine in the intraoperative management of blood loss in patients undergoing TKA.METHODS: This study aimed to evaluate the safety and efficacy of intravenous and intraarticular TXA plus epinephrine in the intraoperative blood management in primary TKA. In this case-control study, 204 patients undergoing primary cemented TKA were enrolled. One hundred two patients received one gr TXA intravenously and intraarticular injection of a mixture containing 500 mg TXA and 0.6 mg epinephrine. They compared to a historical control group comprised of 102 patients that received the same drug combination without epinephrine. The two groups were comparable concerning age, sex, the grade of osteoarthritis, and preoperative hemoglobin and hematocrit.RESULTS: The epinephrine group had significantly higher postoperative hemoglobin (11.70 vs 10.75, p <0.001) and hematocrit (35.70 vs 32.25, p <0.001) compared to the control group at the first postoperative day. The epinephrine group received fewer transfusions, not reaching statistical significance (p =0.110), compared to the control group during hospitalization. The rate of complications was similar between the groups. The combined use of TXA and epinephrine was positively associated with a smaller postoperative hemoglobin drop.CONCLUSION: The combination of intravenous and intraarticular TXA plus epinephrine was safe and reduced the drop of hemoglobin at the first postop day but not significantly the rate of transfusions, in patients undergoing primary TKA. Future higher-level of evidence studies are needed to validate these results. HIPPOKRATIA 2018, 22(2): 86-90.