Aims. Antifibrinolytic agents, including tranexamic acid (TXA) and epsilon-aminocaproic acid (EACA), have been shown to be safe and effective for decreasing perioperative blood loss and transfusion following total hip arthroplasty (THA) and total knee arthroplasty (TKA). However, there are few prospective studies that directly compare these agents. The purpose of this study was to compare the benefits of intraoperative intravenous TXA with EACA. Patients and Methods. A total of 235 patients (90 THA and 145 TKA) were enrolled in this prospective, randomized controlled trial at a single tertiary-care referral centre. In the THA cohort, 53.3% of the patients were female with a median age of 59.8 years (interquartile range (IQR) 53.3 to 68.1). In the TKA cohort, 63.4% of the patients were female with a median age of 65.1 years (IQR 59.4 to 69.5). Patients received either TXA (n = 119) or EACA (n = 116) in two doses intraoperatively. The primary outcome measures included change in haemoglobin level and blood volume, postoperative drainage, and rate of transfusion. Secondary outcome measures included postoperative complications, cost, and length of stay (LOS). Results. TKA patients who received EACA had greater drainage (median 320 ml (IQR 185 to 420) vs 158 ml (IQR 110 to 238); p < 0.001), increased loss of blood volume (891 ml (IQR 612 to 1203) vs 661 ml (IQR 514 to 980); p = 0.014), and increased haemoglobin change from the preoperative level (2.1 ml (IQR 1.7 to 2.8) vs 1.9 ml (IQR 1.2 to 2.4); p = 0.016) compared with patients who received TXA. For the THA cohort, no statistically significant differences were observed in any haematological outcome measure. One patient in the EACA group required transfusion. No patient in the TXA group required transfusion. There were no statistically significant differences in number or type of postoperative complications or LOS for either THA or TKA patients regardless of whether they received TXA or EACA. Conclusion. For hip and knee arthroplasty procedures, EACA is associated with increased perioperative blood loss compared with TXA. However, there is no significant difference in transfusion rate. While further prospective studies are needed to compare the efficacy of each agent, we currently recommend orthopaedic surgeons to select their antifibrinolytic based on cost and regional availability. Cite this article: Bone Joint J 2019;101-B:1093–1099