Previous reports, mostly small clinical trials conducted in USA or Europe, indicated that tranexamic acid (TXA) would be effective for reducing blood transfusions after total knee arthroplasty (TKA). However, large scale studies are needed regarding the effectiveness and safety issue of complication events following TKA, especially for the Asian population. We aimed to evaluate the efficacy and safety of TXA use based on data from an elderly population in Taiwan.This was a retrospective population-based study using an inpatient dataset from the nationwide health insurance research database in Taiwan. Patients aged >65 years with a diagnosis of osteoarthritic knee in 2012 were included (n = 10,321). A low-dose intravenous form of TXA (250–1000 mg) was identified perioperatively during the TKA. The surgical outcomes of interest were allogeneic red blood cell transfusion and postoperative 30-day complications.A total of 1205 (11.7%) patients received TXA. Based on a multilevel logistic regression model, we found a 47% odds reduction of blood transfusion without elevating the complications of infection and vascular-related diseases. Furthermore, the drug effect in reducing transfusion was different among hospital levels, and medical centers had a relatively lower transfusion rate.The use of perioperative TXA was an efficient strategy to prevent blood loss after TKA.