Perioperative blood loss is a frequent cause of complications in total hip replacement (THR). The present prospective study assessed the efficacy of tranexamic acid (Exacyl(®)) in reducing blood loss in primary THR associated to rivaroxaban (Xarelto(®)) thromboprophylaxis. Tranexamic acid associated to rivaroxaban reduces blood loss. A prospective case-control study included 70 primary cementless THRs performed by a single surgeon on a standardized technique, between September 2009 and September 2010. Thirty-seven patients received perioperative tranexamic acid; all patients received rivaroxaban thromboprophylaxis. There was no significant difference between the two groups in terms of peroperative blood-loss volume or rates of thromboembolic or ischemic events or hematoma. Postoperative blood loss, D0-5 differential hemoglobinemia and real blood loss (in mL 100% hematocrit) were significantly lower in the tranexamic acid group. No transfusions were required in the tranexamic acid group, versus four in the control group. Tranexamic acid associated to direct anti-Xa (antithrombin-independent) oral anticoagulants was effective in reducing postoperative blood loss, improving hemoglobinemia at 5 days and reducing transfusion rates. The results also confirmed the efficacy of and tolerance for rivaroxaban thromboprophylaxis in primary THR, with no clinical thrombotic events induced by the association of tranexamic acid with rivaroxaban. Tranexamic acid is a simple means of reducing postoperative blood loss in THR, without increased risk of thromboembolism when associated to rivaroxaban thromboprophylaxis. Level III prospective case-control study.