Objective:In comparison to oxytocin alone, researchers wanted to examine how carbetocin and oxytocin plus sublingual misoprostol influenced the estimated and measured amount of blood loss following vaginal birth in women who had blood loss >500 ml.Patients and Methods: 135 women with blood loss greater than 500 mL after vaginal delivery were recruited in the current randomized open-label clinical trial at a tertiary university hospital between April 2019 and December 2022 (NCT03870503), after receiving standard treatments for managing the third stage of labor and signing an informant consent. They were separated into three groups: group 1 received 100 µg of Carbetocin (Pabal Ferring, UK), group 2 received 400 µg of sublingual misoprostol with 20 IU of oxytocin (Syntocinon, Novartis, Switzerland), and group 3 received just 20 IU of oxytocin. Blood loss of 500 milliliters or less following PPH therapy was the main goal.Results: When compared to the carbetocin and oxytocin plus misoprostol groups, the oxytocin group had a substantial drop in hemoglobin concentration and a significant increase in estimated blood loss (P=0.0001,0.0001). The estimated blood loss in the oxytocin plus misoprostol group was significantly lower than in the carbetocin group (P= 0.004). When comparing the carbetocin (13.3 percent) to the oxytocin plus misoprostol group (11.1percent) and the oxytocin (24.4 percent), the incidence of postpartum blood loss >1000 ml was higher in the oxytocin group (P=0.0001).M a n u s c r i p t a c c e p t e d f o r p u b l i c a t i o n 2 Conclusion: oxytocin plus misoprostol is more effective than oxytocin and carbetocin in the management of post-partum blood loss >500 ml after vaginal delivery.