Postpartum haemorrhage (PPH) is the most common cause of obstetrical haemorrhage, accounting for 16% of maternal mortality in India. The standard uterotonic agent used in active management of the third stage of labour (AMTSL) has traditionally been oxytocin or a combination of oxytocin and ergometrine maleate. Misoprostol, a new uterotonic drug has several advantages over oxytocin which makes it suitable for use in peripheral health centers. Hence, we conducted this study with an objective to compare efficacy and safety of per rectal (PR) Misoprostol with intravenous (IV) Oxytocin in prevention of primary PPH. It was a prospective, randomized controlled trial conducted at Vanivilas hospital attached to BMCRI. 200 pregnant women were enrolled in the study and were randomized to receive either IV oxytocin 10IU or PR misoprostol 800μg immediately after delivery of the anterior shoulder of the baby. Efficacy parameters were incidence of primary PPH, mean blood loss, mean haemoglobin deficit and mean haematocrit deficit. Safety profile was noted in both the groups. Incidence of primary PPH was similar in both groups (p= 0.70). There was no significant difference between both groups in terms of mean blood loss (p=0.13), haemoglobin deficit (p=0.63) and haematocrit deficit (p= 0.57). Shivering and fever were more common in the misoprostol than the oxytocin group (p<0.05), but these were mild and self-limiting. In conclusion, PR misoprostol is as efficacious as IV oxytocin, and hence can be preferred in low resource setting areas.