Aim: To compare the use of intra-umbilical vein injection (IUVI) of ergometrine, with the standard oxytocin intramuscular injection for management of third stage of labor. Materials and Methods: Two groups of women who delivered vaginally of a singleton were randomly assigned to receive 0.2 mg of ergometrine diluted in 10 cc of normal saline via the umbilical vein after clamping of the cord, or to receive oxytocin 5 IU intramuscularly, at delivery of anterior shoulder, plus 10 cc saline via umbilical vein for management of third stage of labor. The primary outcome was the amount of blood loss and the duration of third stage of labor. Secondary outcome included: postpartum hemorrhage (PPH), severe PPH (> 1,000 ml), retained placenta necessitating manual removal, and observed side effects. Results: A total of 1,035 women were recruited, 501 actually received 0.2 mg of ergometrine diluted in 10 cc of normal saline via the umbilical vein, group A, and 517 received oxytocin 5 IU at delivery of anterior shoulder plus 10 cc saline via umbilical vein, group B. Seventeen had no records available. No difference was observed between the two groups' demographic data. The amount of blood loss was slightly higher (270 vs. 230 cc, respectively) in the group of patients who received IUVI ergometrine of than those who received parenteral oxytocin ((p = 0.014). There was no statistically significant difference in the number of PPH (both mild and severe) cases between the two groups. However blood transfusion was needed for only one patient who received oxytocin (group B) for PPH. Additional uterotonics were required in both groups with no significant difference (p = 0.077), between the two groups. Manual removal of the placenta was required for 12 retained placentae of group B, as compared to only nine in group A (p = 0.66). Conclusion: There was a minimal significant increase in the amount of blood loss, without increasing the prevalence of PPH. Local injection at the placental site showed a trend to decrease the need for operative intervention (manual removal of the placenta) than traditional use of oxytocin. Future studies are needed.