Article informationBackground: Postpartum hemorrhage [PPH] is considered as the major cause of maternal death worldwide. A Prostaglandin E1 analog, Misoprostol, has been demonstrated to be useful in lowering intra and postoperative blood loss. However, the proper timing of administration is still up for debate.Objective: Comparative study of Prostaglandin E1 analog [misoprostol] administration via two distinct routes: preoperative rectal and intraoperative intrauterine administration to reduce blood loss during and after cesarean delivery.Patients and Methods: This is a randomized clinical trial that involved 100 pregnant women attending Alzhraa University Hospital, all of them were eligible for elective cesarean section. All participants were randomized into two groups: Group [1]: which involved 50 women who received 400 ug misoprostol intrauterine intraoperative, and Group [2]: which involved 50 women who received 400 ug misoprostol rectally preoperative. Results:The two groups were not statistically significant different regarding the amount of blood loss or the occurrence of postpartum hemorrhage P-value [P<0.05]. The Apgar scores were considerably higher in the intrauterine Group compared to the rectal Group at both 1 and 5 minutes. Conclusion:Both preoperative rectal and intraoperative intrauterine administration of Misoprostol [400ug] have the same effect on the amount of blood loss during caesarean delivery; however, it is more convenient to be administrated during caesarean delivery with a safer neonatal outcome.