BACKGROUND: Intra-articular tranexamic acid (TXA) has been proven effective in reducing postoperative bleeding in anterior cruciate ligament reconstruction (ACLR). We aimed to evaluate the effect of intra-articular injection of TXA with different acting times after an ACLR procedure. PATIENTS AND METHODS: Patients receiving ACLR and intra-articular injection of TXA between September 2023 and January 2024 were randomly divided into two groups, with drainage clamped for 4 h (TXA 4 h group) or 8 h (TXA 8 h group). Postoperative drainage output was the primary outcome. The secondary outcomes included the visual analog scale (VAS), grade of hemarthrosis, and International Knee Documentation Committee (IKDC) functional score. The data of another two groups of patients (TXA 2 h group and placebo group) were retrieved from a previous study as historical control groups for subsequent analysis. RESULTS: 121 patients were included. There were no significant differences in drainage output between TXA 4 h and TXA 8 h groups. On postoperative day 3, significantly decreased grades of hemarthrosis were noted in the TXA 8 h group (P = 0.030). There were no significant differences in the VAS at different postoperative time points or in the IKDC scores. Comparison with the placebo and TXA 2 h groups revealed significant reduction in postoperative drainage among the TXA 4 h and 8 h groups. The IKDC scores were significantly worse in the TXA 8 h group compared with the TXA 2 h (P <
0.001) and placebo (P = 0.009) groups. CONCLUSIONS: A 4 h clamping time for intra-articular TXA administration after ACLR may be considered in current practice, as it effectively reduces drainage and pain without negatively impacting functional outcomes. LEVEL OF EVIDENCE: Level III, cohort study.