Postpartum Hemorrhage (PPH) is a life-threatening Obstetric emergency and most common cause of maternal death worldwide. It is responsible for 25% of maternal mortality, mostly from developing countries. WHO recommends that the use of misoprostol will be beneficial in clinical settings where oxytocin is unavailable or could not be preserved. However, there is dearth of evidence on which route of its administration will be optimal in reducing incidence of PPH. AIM: To compare the effectiveness of rectally administered 600µg misoprostol with sublingually administered 600µg misoprostol in reducing incidence of PPH. To also compare the mean blood loss in each group. METHODS: This was a prospective randomized control study that was carried out in Ekiti state tertiary institutions. Two hundred and six paturients who met the inclusion criteria were recruited into the study. They were randomized immediately after delivery into either the sublingual or per rectal route of 600µg misoprostol for third stage of labour management and prevention of postpartum hemorrhage. Pre-weighed Perineal pads and absorbent underlay sheets were applied. Changes in the weight of the pads and underlay sheets were noted after 1st, 4th and 24th hour. Blood loss was calculated based on the blood loss at each of the hour above. All study participants were followed up till 24hours. Incidence of side effects in each group was noted. Greater than 10% change in the peri-partum Pack cell volume was also considered as PPH.