Objective: To assess the efficacy of intravenous tranexamic acid and ethamsylate in reducing blood loss during and after elective lower segment cesarean delivery in patients at high risk for postpartum hemorrhage. Methods: A double-blind, randomized placebo-controlled study was undertaken of women undergoing elective lower-segment cesarean delivery of a full-term pregnancy at high risk for postpartum hemorrhage at Ain Sham University Maternity Hospital in Cairo, Egypt, between January 2019 and October 2019. Patients were randomly assigned (1:1) using computer-generated random numbers to receive either 1 g tranexamic acid and 1 gm ethamsylate or 5% glucose (placebo) just after delivery of the fetus. Prophylactic oxytocin was administered to all women. Preoperative and postoperative complete blood count, hematocrit values, and maternal weight were used to calculate the estimated blood loss (EBL) during the cesarean, which was the primary outcome. Results: Analyses included 32 women in each group. Our results showed that tranexamic acid and ethamsylate significantly reduced bleeding during and after cesarean delivery. The study group's total blood loss (149.22 ± 54.74 ml) was significantly less than the control group (353.75 ± 115.56 ml) (p < 0.001). In our study, postoperative hemoglobin and hematocrit were significantly higher in the study group than the control group (p < 0.001); Reduction in hemoglobin and hematocrit were significantly less in the study group than the control group (p < 0.001). Conclusion: The use of tranexamic acid and ethamsylate during cesarean delivery can significantly reduce blood loss during and after cesarean delivery.