Background Tranexamic acid (TXA) is safe and effective in total knee arthroplasty (TKA) for the prevention of bleeding. However, the role of TXA during unicompartmental knee arthroplasty (UKA) remains unclear. This study aimed to compare operative blood loss in patients undergoing UKA treated with an intra-articular injection of TXA with controls undergoing UKA without TXA. Material/Methods The prospective study included 101 patients who underwent UKA between January 2014 to March 2018. All patients completed a preoperative routine examination and were randomized to the study group (n=54) and the control group (n-47). The study group was given an articular injection of TXA (1.5 g in 50 ml normal saline) after the fascia was closed; the control group was injected with the same volume of normal saline. Blood volumes were measured from the drainage tube of the two groups during 48 hours. Total blood loss, postoperative drainage, hidden blood loss, blood transfusion rates, postoperative hemoglobin values, indicators of coagulation function, and the rates of wound complications were recorded. Results Total blood loss in the study group was 745.6±105.1 ml, total drainage volume was 353.9±79.5 ml, and the hidden blood loss was 391.7±80.5 ml, which were all significantly lower when compared with the control group (P<0.05). None of the patients in the two groups suffered complications of surgery. Conclusions Intra-articular injection of TXA significantly reduced the total blood loss in patients who underwent UKA and did not increase the rate of complications.