The objective of this study was to ascertain whether combined intravenous (IV) and intra-articular (IA) administration of tranexamic acid (TXA) is beneficial for reducing blood loss and the prevalence of deep venous thrombosis (DVT) in primary simultaneous bilateral total knee arthroplasty compared with IV only administration of TXA. One hundred fifty-four patients received a combined IV and IA injection of TXA in 1 knee and an IV only injection of TXA in the other. Transfusion rates and volumes and the amount of blood loss were recorded at 8 hours, 24 hours, and 48 hours. In addition, the authors ascertained whether the prevalence of DVT was higher in the patients with combined IV and IA administration of TXA than in the patients with IV only administration of TXA. Overall total blood loss was not significantly different (299.6 mL vs 280.1 mL, P=.22) between the 2 groups. The prevalence of DVT was 11% (17 knees) in the combined IV and IA group and 14% (22 knees) in the IV only group. This difference was not significant (P=.25). Combined IV and IA administration of TXA in bilateral total knee arthroplasty has no additional benefit in reducing total blood loss when compared with IV only administration. The prevalence of DVT was low and not significantly different between the 2 groups. Furthermore, no pulmonary embolism was found in either group.