Objective To investigate the effect of Tranexamic Acid injection on blood loss during the perioperative period of total knee arthroplasty. Methods A total of 147 cases undergoing primary unilateral total knee arthroplasty with rheumatoid arthritis or osteoarthritis were selected from March 2015 to August 2015. According to random number table, all of the patients were randomly divided into single use group,repeated use group and control group, with 49 cases in each group. The single use group was given tranexamic acid 10 mg/kg by intravenous drip half an hour before surgery, the repeated use group was given the same one half an hour before surgery and Tranexamic Acid 50 ml by intramuscular injection in periprosthetic tissue after surgery. The control group was not given tranexamic acid injection. Hidden blood loss, total blood loss, intraoperative blood loss, volume of postoperative drainage, the ratio of blood transfusion,the incidence of pulmonary embolism and the incidence of deep vein thrombosis were compared among the three groups. Results The volume of postoperative drainage, the intraoperative blood loss, the hidden blood loss and the postoperative total blood loss in the single use group were significantly lower than those in the control group, but significantly higher than those in the repeated use group (P < 0.05); the ratio of blood transfusion in the single use group and the repeated use group was significantly lower than that in the control group (x2= 3.984 and 5.482,p < 0.05), but was significantly higher than that in the repeated use group (x2=8.182, p< 0.05). No pulmonary embolism or deep vein thrombosis was occurred in each group. Muscular venous thrombosis was found 4 cases in the single use group and 3 cases in the repeated use group and the control group, but there was no significant difference among the three groups (x2 = 0.173, p> 0.05). Conclusions Tranexamic Acid injection can reduce the amount of bleeding and the ratio of blood transfusion in patients with total knee arthroplasty, but will not increase the incidence of pulmonary embolism or deep vein thrombosis.