To compare outcomes in males given perioperative tranexamic acid (TXA) during holmium laser enucleation of the prostate (HoLEP) to a historical cohort that did not receive TXA. Our cohort included HoLEP patients (N=1037) from August 2018 through November 2022. Exclusion criteria included history of stroke, transient ischemic attack, or coronary stent placed within 18 months. The primary predictor was TXA during HoLEP. The primary outcome variable was a return to the operating room (RTOR) for bleeding. Secondary outcomes included catheter reinsertion, transfusion, and clotting complications. Multivariable models evaluating associations of TXA with outcomes were adjusted for potential confounders. In our cohort, 214/1035 had one or more complications with 81 having a Clavien-Dindo Grade of 3a or higher, 114/1037 with catheter reinsertion, 36/1037 RTOR for bleeding, and 15/1035 had a transfusion. TXA use was not associated with 30-day RTOR. 3.7% of those without TXA had a RTOR, and 3.1% of those with TXA had a RTOR (adjusted odds ratio 0.63, 95% CI 0.28-1.38, P=.25). Transfusion rates were higher for those without TXA (2.0%) compared to with (0.5%). This was statistically significant after adjustment (adjusted odds ratio 0.13, 95% CI 0.03-0.69, P=.016) and after correction for multiple testing (corrected P=.048). TXA use was not associated with catheter reinsertion or clotting complications. Routine perioperative intravenous TXA in HoLEP patients was not associated with a reduction of RTOR for bleeding, catheter reinsertion, or clotting complications. TXA was associated with decreased transfusions with a low overall event rate of 1.4%.