Acute peri-operative blood loss warranting transfusion is a frequent consequence of major joint replacement (TJR) surgery. Significant peri-operative anemia can contribute to hypotension, dyspnea, coronary ischemia and other peri-operative medical events that can result in increased risk of peri-operative complications, readmissions and impair the patient's ability to mobilise after surgery resulting in a longer length of stay (LOS) and increase skilled nursing facility (SNF) utilization. The risks associated with allogeneic blood transfusions (ABT) administered to treat symptomatic peri-operative anemia are numerous and extend beyond the concerns of transmission of communicable disease (HIV, hepatitis, other). Patients receiving ABTs have been shown to have a longer hospital LOS, higher risk of infection, and higher mortality after TJR than those who do not require transfusion after surgery. As a result, many different pre-operative, peri-operative and post-operative strategies have been utilised to minimise peri-operative blood loss and transfusion need for patients undergoing TJR. Several studies have shown that the strongest predictor of the need for ABT in the TJR patient is the pre-operative hematocrit (Hct). As a result, all patients with unexplained pre-operative anemia should be evaluated for an underlying cause prior to elective TJR surgery. In recent years, focus has shifted towards peri-operative reduction of blood loss with the use of pharmacologic agents like tranexamic acid (TXA). These agents work by inhibiting fibrinolysis and activating plasminogen. Numerous studies have shown that TXA given IV, applied topically into the surgical wound or given orally have been shown to reduce peri-operative bleeding and ABT after both THA and TKR. Regardless of route of administration, all appear to be more efficacious and considerably more cost-effective in reducing the need for ABT than other methods discussed previously. Despite concerns about the potential increased thromboembolic risk in patients undergoing TJR, there does not appear to be any conclusive evidence suggesting an increased risk of venous thromboembolic disease (VTED) in TJR patients who receive peri-operative TXA. Although it may be unnecessary, many TJR surgeons still, however, avoid use of TXA in patients with a past history of VTED, stroke, coronary artery disease (including coronary stents), renal insufficiency, hypercoagulable state and seizure disorder. The use of topical TXA may be safer in some of these high risk patients since systemic absorption is minimal when administered via this route. Although the optimal method of administration (IV, topical, oral or combined) has not yet been determined based on safety, cost and reduction of need for ABT, incorporation of tranexamic acid into a blood conservation program is clearly the standard of care for all TJR programs that should nearly eliminate the need for ABT for patients undergoing TJR