Background and Objective: Postpartum hemorrhage ranks among the most leading causes of maternal morbidity and mortality in the world. Intravenous oxytocin is routinely used to reduce postpartum hemorrhage. The aim of this study was to compare the effect of 400 µg of oral misoprostol versus 10 IU of intravenous oxytocin in preventing postpartum hemorrhage. Materials and Methods: This randomized clinical trial, which was conducted at the Kosar Hospital in Qazvin, included 269 pregnant women. Inclusion criteria were: singleton pregnancy, over 37 weeks of gestation parity of less than 3 vertex presentation spontaneous or induced labor and an estimated fetal weight under 4 kg. Exclusion criteria included: history of postpartum hemorrhage asthma coagulopathy and anticoagulant consumption presence of placental abruption postpartum hemorrhage due to lacerations instrumental delivery and cesarean section. Selected patients randomly received either 400 µg of oral misoprostol or 10 IU of intravenous oxytocin after delivery of the anterior shoulder or within the first minute after the delivery. Hemoglobin and hematocrit were measured both during admission and 24 hours after the delivery and were compared together. Results: Postpartum hematocrit drop occurred in 3.33% +3.44 of the participants in the oxytocin group compared with 2.81% +1.26 in the misoprostol group. The rate of using additional oxytocin was 34.8% in the oxytocin group versus 20.5% in the misoprostol group. Fever occurred in 2 of the women in the misoprostol group. Conclusion: Administration of 400 µg oral misoprostol appears to be as effective as 10 IU of intravenous oxytocin in reducing the blood loss after delivery.