Background: Tranexamic acid (TXA) is an antifibrinolytic agent used to reduce bleeding in major surgical procedures. This study evaluates the efficacy and safety of the systemic and topical intra-articular administration of TXA in total hip arthroplasty (THA). Methods: Patients (N = 123) scheduled for primary unilateral THA were divided into 3 treatment groups: control group; TXA, systemic, repeated 1 g bolus; TXA, topically intra-articularly, 2 g in 50 mL saline. Primary readouts used were intra- and postoperative bleeding, transfusion requirement, postoperative hemoglobin levels and complications. Results: Both systemic and topical intra-articular TXA administrations decreased bleeding and transfusion requirements. Topical intra-articular use of TXA led to the reduction in intraoperative and postoperative bleeding and affected hemoglobin levels compared with control. Systemic administration of TXA led to a significant reduction of postoperative bleeding and transfusion rate compared with control and was not different in efficacy and complication incidence when compared to topical administration of TXA. Conclusions: The use of TXA to reduce blood loss and transfusion requirements in THA is an effective and safe concept in practice. The dose of 2 g TXA topically intra-articularly and a repeated bolus of 1 g TXA systematic led to lower intra- and postoperative bleeding and a significantly lower transfusion rate than the control group. Topical intra-articular TXA administration could be a reasonable alternative in high-risk patients.