Background: Intraoperative hemostasis should be performed with great caution because bleeding is a huge enemy of patient safety during surgery. Tranexamic acid is a lysine synthetic derivate that inhibits fibrinolysis and diminishes the bleeding by blocking the five lysine-binding sites for plasminogen. The authors compare the efficacy of tranexamic acid versus placebo as a hemostatic agent in liposculpture procedures. Methods: The authors conducted a multicenter, double-blind, randomized, controlled clinical trial in patients who were scheduled for liposculpture in three plastic surgery centers (Colombia and Mexico) between January of 2019 and February of 2020. One hundred forty-one patients were randomly assigned into three groups: intravenous (1 g of tranexamic acid), subcutaneous (1 g of tranexamic acid), and placebo (normal saline). Forty-seven patients were assigned to each group. There were 30 male patients and 111 female patients. The main outcome was to evaluate the amount of postoperative bleeding between groups. The primary outcome was measured by the hemoglobin point loss at day 1 (preoperative hemoglobin minus hemoglobin at day 1 postoperatively) and the hemoglobin (in milligrams per deciliter) point loss at day 5 (preoperative hemoglobin minus hemoglobin at day 5 postoperatively). Results: The authors found the intravenous intervention group to have a greater hemoglobin level than the other two groups on both the first postoperative day (p = 0.0001) and the fifth postoperative day (p = 0.001). There were no statistical differences in hemoglobin values between the placebo and the subcutaneous intervention groups. Conclusion: Intravenous tranexamic acid is a good therapeutic choice to implement on liposculpture procedures to decrease postoperative bleeding. Clinical Relevance Statement: The preoperative use of intravenous tranexamic acid not only decreases the bleeding rate after liposuction procedures, but also allows greater lipoaspirate volumes when performing high-definition liposculpture. Further studies are required to support the effectiveness of tranexamic acid within the infiltration solution. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.