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Background: Bleeding and bleeding-related complications remain common after bipolar transurethral resection of the prostate (TURP) for benign prostatic hyperplasia. This may possibly lead to prolonged postoperative irrigation, catheterization, and hospital stay. The objective of this trial was to evaluate the effect of high-dose tranexamic acid (TXA) on perioperative blood loss in patients treated with bipolar TURP for prostate sizes between 30 and 80 g., Methods: We conducted a single-center, prospective, double-blind, randomized controlled trial. Eighty patients were screened for inclusion between March 2020 and January 2023. After exclusion, 65 patients were randomized in two comparable groups. The TXA group (31 patients) received a TXA intravenous loading dose of 10 mg/kg over 30 min before induction, followed by a maintenance dose of 5 mg/kg/h over 12 h. The placebo group (34 patients) received an equal dose of saline infusion. We measured age, weight, preoperative prostate size, anticoagulant use, 5-alpha reductase inhibitor use, preoperative urinary tract infection, American Society of Anesthesiologists score, difference in pre- and 24 h postoperative hemoglobin and hematocrit levels, operative time, resected adenoma weight, duration of postoperative irrigation, total amount of postoperative irrigation fluid, indwelling catheter time, duration of hospital stay, blood transfusion rate, and 4-week complication rate., Results: Baseline characteristics in both groups were comparable. Postoperative hemoglobin decrease in TXA versus placebo group was 1 versus 1.6 mg/dL, respectively (p = 0.04). In addition, the amount of postoperative irrigation fluid (10.7 vs. 18.5 L), irrigation time (24.3 vs. 37.9 h), catheterization time (40.8 vs. 53.7 h), and hospital stay (46.9 vs. 59.2 h) were statistically significant in favor of TXA use. No blood transfusions were carried out. Four-week complication rate was comparable between the two groups., Conclusions: Perioperative high-dose TXA seems beneficial in reducing hemoglobin loss, postoperative irrigation, catheterization time, and hospital stay in bipolar TURP for prostate sizes between 30 and 80 g, without increased risk of TXA-related thromboembolic events., (© 2023 Wiley Periodicals LLC.)