Comparative efficacy and safety of intra-articular versus intravenous tranexamic acid in primary total knee arthroplasty: a systematic review and meta-analysis

Total knee arthroplasty (TKA) is frequently associated with considerable perioperative and postoperative blood loss, making tranexamic acid (TXA) a key component of modern blood-sparing protocols. Although both intravenous (IV) and intra-articular (IA) routes are widely used, the optimal administration method remains debated owing to differences in efficacy, systemic exposure, and thromboembolic risk. To compare the efficacy and safety of IA versus IV TXA in primary TKA, focusing on blood loss, postoperative hemoglobin and hematocrit, drain output, hospital stay, transfusion requirement, and thromboembolic and wound complications. A systematic search of PubMed, Web of Science, and Google Scholar was performed on July 31, 2026, following PRISMA 2020 guidelines. Randomized controlled trials comparing IA and IV TXA in primary TKA were included. The primary outcomes were total blood loss, hemoglobin level, hematocrit level, total drain output, and mean length of hospital stay. Secondary outcomes included transfusion requirements and adverse events. The risk of bias was assessed using the Cochrane ROB 2.0 tool. Twenty-three randomized controlled trials met the inclusion criteria. Compared with intravenous administration, intra-articular TXA was associated with lower total blood loss (p = 0.004) and reduced drain output (p = 0.04); however, both outcomes showed substantial between-study heterogeneity (I 2 = 87% and 93%, respectively), driven largely by variability in TXA dose, timing, and tourniquet protocol across the included studies. No significant differences were observed between the IA and IV TXA groups in terms of postoperative hemoglobin, hematocrit, transfusion requirements, hospital stay, or complications such as deep vein thrombosis (DVT), pulmonary embolism (PE), or wound infection. Intra-articular TXA was associated with statistically significant, though modest, reductions in blood loss and drain output compared with intravenous administration, with a comparable safety profile between routes. Given the substantial heterogeneity in TXA dosing and administration protocols across the included studies, these findings should be interpreted as hypothesis-generating rather than definitive evidence of a route-specific effect, and do not yet support IA administration as a superior alternative to IV TXA. Larger, protocol-standardized multicenter trials are needed to determine whether the route of administration independently influences outcomes.