BACKGROUND: Although prophylactic tranexamic acid administration at cesarean delivery resulted in a lower incidence of calculated estimated blood loss > 1000 mL or red-cell transfusion by day 2, its failure to reduce the incidence of hemorrhage-related secondary clinical outcomes (TRAAP2 trial) makes its use questionable. The magnitude of its effect may differ in women at higher risk of blood loss, including those with multiple pregnancies. OBJECTIVE: To compare the effect of tranexamic acid vs placebo to prevent blood loss at cesarean delivery among women with multiple pregnancies. STUDY DESIGN: Secondary analysis of the TRAAP2 trial data including 319 women with multiple pregnancies in this double-blind, randomized controlled trial from March 2018 through January 2020 in 27 French maternity hospitals. Women with a cesarean before or during labor at 34 or more gestational weeks were randomized to receive intravenously 1 g of tranexamic acid (n=160) or placebo (n=159), both with prophylactic uterotonics. The primary outcome was a calculated estimated blood loss > 1000 mL or a red blood cell transfusion by 2 days after delivery. Secondary outcomes included clinical and laboratory blood loss measurements. RESULTS: Of the 4551 women randomized in this trial, 319 had a multiple pregnancy and cesarean delivery, 298 (93.4%) with primary outcome data available. This outcome occurred in 62 of 147 women (42.2%) in the tranexamic acid group and 67 of 152 (44.1%) receiving placebo (adjusted risk ratio, 0.97; 95% CI 0.68-1.38; P=.86). No significant between-group differences occurred for any hemorrhage-related clinical outcomes: gravimetrically estimated blood loss, provider-assessed clinically significant hemorrhage, additional uterotonics, postpartum blood transfusion, arterial embolization, and emergency surgery (P>.05 for all comparisons). CONCLUSION: Among women with a multiple pregnancy and cesarean delivery, prophylactic tranexamic acid did not reduce the incidence of any blood loss-related outcomes.Read less <