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Aim: The aim of this study was to evaluate the efficacy of adjunctive rectal misoprostol compared to oxytocin infusion in the prevention of primary postpartum hemorrhage after routine active management of the third stage of labor in women with identifiable risk factors for uterine atony., Material and Methods: A double-blind randomized controlled trial was carried out at Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria. A total of 264 parturients with known risk factors for postpartum hemorrhage were randomized to receive either rectal misoprostol (600 µg; n = 132) or oxytocin infusion (20 IU in 500 mL; n = 132) after routine active management of the third stage of labor. Intrapartum blood loss was measured using a combination of the BRASSS-V calibrated drapes and differential pad weighing. Hematocrit was measured intrapartum and 24 h postpartum., Results: There was no significant difference (P = 0.07) in the mean intrapartum blood loss between the misoprostol (387.28 ± 203.09 mL) and oxytocin (386.73 ± 298.51 mL) groups. There was also no difference in the requirement for additional intervention for uterine atony (P = 0.74). Postpartum hematocrit drop and blood transfusion were, however, significantly less in the misoprostol group., Conclusion:  Rectal misoprostol is as effective as oxytocin infusion as an adjunct for prevention of postpartum hemorrhage in women with risk factors for uterine atony and is associated with a lower hematocrit drop and blood transfusion postpartum. However, shivering, pyrexia and vomiting are more frequent with misoprostol, though usually self-limited., (© 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.)