Objective: To determine the most efficient route and timing of oxytocin administration for active management of the third stage of labor. Methods: A prospective randomized study was done at one center in Ankara, Turkey, between January and October 2010. Women with a singleton pregnancy (>37 weeks) who had a live vaginal birth were randomly allocated to four groups: iv-A (intravenous oxytocin after delivery of the fetus), iv-B (when anterior shoulder seen), im-A (intramuscular oxytocin after delivery), and im-B (when anterior shoulder seen). Postpartum blood loss within the first hour, hemoglobin, hematocrit, and duration of the third stage were compared. Results: A total of 600 eligible women were recruited; 150 were assigned to each group. Postpartum blood loss, prepartum and postpartum hemoglobin and hematocrit, and need for additional uterotonics were similar among groups (P> 0.05). The duration of the third stage of labor and changes in hemoglobin and hematocrit were significantly reduced in group iv-B (P < 0.05). Among women not exposed to oxytocin before delivery, postpartum blood loss was significantly lower in group iv-B (P = 0.019). Labor augmentation was related to significantly increased postpartum blood loss in all groups except iv-A. Conclusion: Although postpartum blood loss was similar in all groups, early intravenous administration seemed to have beneficial effects. (C) 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.