Background: Postpartum haemorrhage (PPH) is one of the major causes of maternal mortality globally. About 14 million patients suffer from postpartum haemorrhage annually worldwide, of which about 140,000 die. The active management of third stage of labour with the use of uterotonic drugs has reduced the risk of postpartum haemorrhage significantly. The most common uterotonic drug currently in use is oxytocin but the problem of insufficient skilled manpower for its administration, inadequacy of electric power supply to ensure the stability of the drug at appropriate temperature, and its high cost have made widespread use of oxytocin difficult in the resource-poor countries. This has made the search for an effective, affordable, stable and available alternative necessary. Misoprostol, an analogue of prostaglandin-E1, has a good uterotonic activity, is highly affordable, does not require specialized skill to administer and is very stable at room temperature. It also has multiple routes of administration, which makes its use in resource-poor countries indispensable. Aim: To determine if there is any difference in the efficacy of intravenous oxytocin over oral misoprostol in the prevention of primary postpartum haemorrhage. Study Design: This was a prospective, double-blinded, randomized study of uncomplicated pregnant women who had vaginal delivery in ESUT Teaching Hospital, Enugu. Sample Size: Two hundred (200) pregnant women who satisfied the inclusion criteria were recruited in this study with each arm of the study accommodating 100 participants. Methodology: The eligible women were recruited on presentation to the labour ward after giving their consent. They were randomly allocated into 2 groups: A and B. Group A received 2 tablets (400mcg) of oral misoprostol and 1mililtre (ml) of sterile water intravenously while group B received 2 tablets of white vitamin c and 1ml (10iu) of intravenous oxytocin immediately after cord clamping and cutting following the delivery of the baby. Pre-weighed delivery mats and vulval pads were used to collect the blood at delivery and for the first 24 hours for weighing and estimation of blood loss. A proforma was used to record the necessary data. Statistical Analysis: Data collected from the study was analyzed with the Statistical Package for Social Sciences (SPSS) computer software version 20.0 for windows. Statistical analysis was both descriptive and inferential at 95% confidence level. The socio-demographic variables were used to categorize the data and this was subjected to comparative statistical evaluation to yield frequencies, means, and percentages. Test of significance between class differences was by Pearson’s Chi-square test for categorical variables and student’s t-test for continuous variables. All P<0.05 at one degree of freedom (df=1) was considered statistically significant. Results: Two hundred pregnant women were recruited into the study with 100 women on each arm and all completed the study. The amounts of blood loss (in mililitre) in the misoprostol and oxytocin arms were 339.36 ± 122.28 and 378.52 ± 148.24, respectively. Forty-three women had PPH (blood loss ≥ 500ml) but there was no significant difference in the amount of blood loss and occurrence of PPH on both arms of the study. Conclusion: There was no difference in the efficacy of oxytocin over misoprostol in the management of the 3rd stage of labour for preventing PPH. We therefore, recommend that misoprostol can be adopted as an alternative/substitute to oxytocin in the management of the third stage of labour especially in the developing countries for prevention of PPH.