Objective: Postpartum hemorrhage is a major obstetrical complication and one of the important but preventable causes of maternal morbidity and mortality. The aim of the study is to compare the efficacy of syntometrine versus oxytocin in the active management of third stage of labor in reducing the risk of PPH and other adverse third stage outcomes. Methodology: This is a randomized prospective comparative study conducted from September 2008 to August 2009 at the department of Obstetrics and Gynecology, Institute of Social Obstetrics and Govt. Kasturba Gandhi Hospital for Women and Children, Chennai, on 300 patients. The patients were assigned to 2 groups at random of 150 patients in each group. All pregnant women with singleton pregnancy of 20-35 years of age with no known risk factor for PPH were included. Exclusion criteria observed for patients with previous caesarean section, previous scarred uterus, multiple pregnancy, Cardiac patient, hepatic disorders, disorders of blood coagulation. The data was analyzed using t test and chi square test. Results: The mean blood loss in syntometrine group was 120ml and oxytocin group was 171ml. The difference of mean blood loss between two group was 51ml, which is statistically significant (p=0.000). Conclusion: It is concluded from this study that the use of syntometrine as part of routine AMTSL (Active Management of Third Stage of Labor) appears to be associated with a statistically significant reduction in mean blood loss when compared to Oxytocin.