Background: Postpartum hemorrhage (PPH) and intra-operative blood during cesarean delivery is a major concern to all obstetricians, misoprostol is a prostaglandin E1 analogue with good uterotonic properties and has been evaluated for both prevention and treatment of postpartum haemorrhage.  Objective: To compare between intrauterine and sublingual misoprostol for the prevention of intra and postoperative uterine atonic bleeding in cesarean delivery. Patients and methods: This study was a randomized controlled clinical trial. This study was carried out at conducted in the operative rooms of Bab Al-Sharia Maternity Hospital, Obstetrics and Gynecology Department, Al-Azhar University, from July 2020 till January 2021. Two hundred pregnant women were recruited from the operative rooms of Bab- Al Sharia Maternity Hospital, Obstetrics and Gynecology Department, Al-Azhar University. Result: There were insignificant difference between both groups as regards age, gravidity, parity, abortion, gestational age (in weeks), risk factor and previous surgery and side effects. There was significant difference between both groups as Blood loss (Intra-operative, Post-operative and overall. Conclusion: Intrauterine misoprostol (600 mg), is effective in decreasing the incidence of PPH and reducing the amount of postpartum blood loss. Also, it reduced the need for blood transfusion, the extra ecbolics, and additional intervention and with less reduction in postoperative hemoglobin (HB) level and hematocrit level when compared to oxytocin alone.