BACKGROUND The leading causes of pregnancy-related deaths are haemorrhage, embolism and hypertensive disorders of pregnancy. Postpartum haemorrhage is a major preventable cause of maternal morbidity and mortality in developing countries. 1 Uterine atony is the main cause of PPH. Therefore, to reduce PPH, we have to address the role of uterotonics. In this context, addition of misoprostol along with WHO recommended 10 units oxytocin in active management of third stage of labour may play an important role. This study was conducted with the aim of comparing the efficacy of Misoprostol plus oxytocin versus oxytocin only for the prevention of post-partum haemorrhage. METHODS This randomized controlled trial was performed at R. G. Kar Medical College and Hospital to compare the efficacy of misoprostol along with oxytocin for the prevention of post-partum haemorrhage (PPH) with oxytocin only in the third stage of labour to prevent of postpartum haemorrhage. 600 women without risk of PPH were randomly allocated to receive either 600 mcg orally, misoprostol along with 10 units of oxytocin intramuscularly (Group I) or 10 units of oxytocin intramuscularly (Group II) within 1 minute of delivery, 300 in each group. The efficacy and the safety of these two drugs were analysed on the basis of percentages fall in haemoglobin (Hb) from pre delivery to 48 completed hours after delivery and also need for blood transfusion. RESULTS 600 mcg orally misoprostol along with 10 unit of oxytocin intramuscularly is better than 10 units of oxytocin intramuscularly to control PPH with minimal side effects. CONCLUSIONS 600 mcg oral misoprostol along with 10 units of oxytocin intramuscularly may be recommended in place of 10 units of oxytocin intramuscularly to control PPH.