Background: Postpartum hemorrhage (PPH) is considered the most common cause of mortality in cesarean section (CS), and vaginal deliveries and to intercept the uterine bleeding and atony in CS there is need for oxytocin.  Objective: This study aimed to reduce the incidence of primary postpartum hemorrhage after cesarean section (CS) by using either intravenous oxytocin or intrauterine misoprostol. Patients and methods: This study was conducted on 76 cases full term pregnant female patients with no risk factors for postpartum hemorrhage. They were admitted for elective caesarean section at Zagazig University Hospital. They were divided into two groups regarding the protocol of treatment, oxytocin group (A) was given oxytocin 10 IU in 250 ml of normal saline solution intravenous over 10 minutes directly after delivery of the fetus. Group (B) included 38 cases that were administered 400 mcg misoprostol intrauterine after delivery of placenta. Results: There was statistically significant variation between the groups of the present study concerning blood loss with higher blood loss either intraoperative, postoperative and overall blood loss in intrauterine misoprostol group than in intravenous oxytocin group. There was a significant difference between the two studied groups concerning side effects of drugs with higher shivering among intrauterine misoprostol group, while headache, and vomiting were reported in the group of oxytocin.Conclusion: Intravenous oxytocin infusion considered more potential than intrauterine misoprostol in blood loss reduction in CS.