Background: Tranexamic acid (TA) use in lower-limb arthroplasty has been valued in these surgeries high-risk hemorrhagic due to its antifibrinolytic action. The objective of the present study was to determine the effectiveness of the combined intravenous (IV) and intraarticular (IA) administration of TA in lower-limb arthroplasty. Methods: We conduct a prospective observational study between January 1, 2014, and December 31, 2017, including all programmed lower-limb arthroplasties. Patients were divided into four groups: no TA, 15 mg/kg IV TA, 3 g IA TA, and 15 mg/kg IV and 3 g IA. The effect on calculated total blood loss (milliliter of red blood cell [RBC]), hemoglobin, transfusion, and duration of hospitalization was studied after adjustment on age, American Society of Anesthesiologists, surgery, and postoperative curative anticoagulation. Complications related to TA administration were systematically reported. Results: A total of 1909 patients were included - "no TA," n = 184; "IV," n = 1137; "IA," n = 214; and "IV + IA," n = 374. In the IV + IA group, a decrease in blood loss was observed compared to the no TA group (+220 ml 95% confidence interval [CI] [184; 255] of RBC P < 0.001) and in the IA group (+65 ml 95% CI [30; 99] of RBC P < 0.001). The length of hospital stay of the IV + IA group was shorter compared to the no TA group (hazard ratio [HR] 0.35, 95% CI [0.29; 0.43], P < 0.001) to the IA group (HR 0.57, 95% CI [0.48; 0.69], P < 0.001) and the IV group (HR 0.45, 95% CI [0.39; 0.50], P < 0.001). One case of deep vein thrombosis occurred in the group without TA. Conclusion: Administration of combined TA appears effective and safe; further studies are needed in order to establish a consensual protocol.