Postpartum hemorrhage is a life threatening situation and one of the important causes of maternal mortality and morbidity, worldwide. To evaluate the effectiveness of a low dose (400ug) of misoprostol administrated sublingually compared to 10 IU of intramascular oxytocin for the reduction of postpartum blood loss. A total of 120 patients were randomized to receive either 400μg misoprostol sublingually or 10 IU oxytocin intramuscularly after vaginal delivery. Primary outcome measured was mean blood loss and incidence of primary postpartum hemorrhage (PPH). Secondary outcome measured included change in pre and 24 hour post-delivery hemoglobin and hematocrit values, side effects of the used drugs, and the need for blood transfusion. Results: Although not statistically significant, mean blood loss mean in misoprostol group (301.92 ±132.95) was lower than in oxytocin group (317.58 ±120.12). Incidence of postpartum hemorrhage was (1.7%) in misoprostol group versus in oxytocin group (3.3%). We observed that 6.7% and 8.3% of women experienced a hemoglobin decline of >10% 24 hours after receiving misoprostol and oxytocin, respectively (p = 1.0), the mean of HCT drop in misoprostol group (3.43 ±2.8) and (3.38 ± 2.92) in oxytocin group ( p = 0.92) . Side effects were significantly greater in the misoprostol group than in the oxytocin group. Conclusion: Although not statistically significant, 400 ug of sublingual misoprostol is more effective than 10 IU of oxytocin administrated via the intramuscular route in reducing post delivery blood loss.