ABSTRACT Post-partum hemorrhage (PPH) is a common cause of maternal mortality in developing countries. Active management of postpartum hemorrhage by an uterotonic drug decreases the rate of postpartum hemorrhage. Studies suggest that the use of misoprostol may be beneficial in clinical settings where oxytocin is unavailable. The aim was to compare the safety and efficacy of oxytocin and misoprostol when used in the prevention of PPH. It is a double-blind study with 200 pregnant women who had a vaginal delivery were assigned 100 allocated in each groups of patients receiving either 800μg of misoprostol, rectally, or 5 IU of intravenous oxytocin, after delivery of the baby. Intra-operative bleeding, hemoglobin level before and 24 hour after operation, blood pressure before and after the administration of the drugs, and adverse drug effects were noted. The quantity of blood loss was high in the oxytocin group in comparison to the misoprostol group. There was no significant difference in the decrease in hematocrit and hemoglobin between the two groups. Although there was no significant difference in the need for transfusions and uterotonics between the two groups. Fever and chills are significantly higher among misoprostol patients. Study indicates that misoprostol may be considered as an alternative for oxytocin in low resource clinical settings.