The aim of this trial was to evaluate the efficacy and safety of intra-articular administration of tranexamic acid (TXA) plus diluted-epinephrine (DEP) on perioperative blood loss and transfusion in primary unilateral total knee arthroplasty (TKA) without drainage. One hundred patients scheduled to undergo TKA were randomized into two groups: 50 patients received intra-articular 3g TXA plus 0.25mg DEP (1:200,000), and 50 patients received 3g topical TXA alone. The results showed that topical combined administration significantly reduced total blood loss (P=0.006), hidden blood loss (P=0.000) and transfusion rate (0% vs. 4%), without increasing the risk of thromboembolic and hemodynamic complications (P>0.05). Therefore, topical TXA plus DEP was effective and safe in reducing blood loss and transfusion following TKA, without substantial complications.