Purpose: The purpose of this study was to examine the effectiveness of tranexamic acid administration for the prevention of postpartum hemorrhage in women with high-risk pregnancies. Tranexamic acid, with the recommended oxytocin, was administered in the third stage of labor to reduce vaginal blood loss and prevent postpartum hemorrhage.Methods: A double-blind randomized placebo-controlled trial with two parallel groups was conducted in women scheduled to undergo vaginal delivery at the Maternity Teaching Hospital, Erbil City, Kurdistan region, Iraq. The women were randomly assigned to receive tranexamic acid (97 women) or placebo (99 women) with oxytocin immediately after fetal delivery in the third stage of labor. We measured vaginal blood loss from fetal to placental delivery and the time from fetal to placental delivery.Results: The mean blood loss in the oxytocin alone group (group 1) was significantly higher than that in the tranexamic and oxytocin group (group 2). The incidence of postpartum hemorrhage (blood loss of ≥500 mL) and blood loss of ≥250 mL was significantly higher in group I than in group 2. The length of the third stage of labor was significantly longer in group 1 than in group 2.Conclusions: In the women who delivered vaginally and had risk factors of postpartum hemorrhage, the incidence rates of the primary outcome of postpartum hemorrhage and blood loss of <250 mL, and the time to placental delivery were significantly lower in the women who received tranexamic acid with active management of third stage labor than in those who received placebo.Trial registration number: ClinicalTrials.gov ID: NCT04201951, December 17, 2019