Objective: To assess the effectiveness of 800 mu g of rectal misoprostol compared with an intravenous infusion of 5 IU of oxytocin as prophylaxis against postpartum hemorrhage (PPH). Methods: A total of 514 women in labor were randomized into two groups (257 women in each). Within I minute of delivery of the anterior shoulder participants in group I received 800 mu g of rectal misoprostol and I ampoule of normal saline in 5 mL lactated Ringer solution intravenously; group 2 received a rectal placebo tablet and 5 IU of oxytocin in 5 mL lactated Ringer solution intravenously. Results: Both groups were comparable regarding the need for uterotonics, blood transfusion, and hematocrit drop of 10% or greater, 24 hours post partum (P = 0.54. P = 0.25, and P = 0.85, respectively). Fever was significantly higher among misoprostol patients (18.7% vs 0.8%, P < 0.001). Conclusions: Routine use of 800 mu g of rectal misoprostol was effective in reducing blood loss after delivery. We recommend the regimen for low-resource, busy obstetric settings. (C) 2009 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.