OBJECTIVES: To assess the cost-effectiveness of carbetocin versus oxytocin for prevention of postpartum hemorrhage (PPH) from uterine atony after vaginal delivery/ cesarean section in women with risk factors for developing bleeding. METHODS: A decision tree was developed for vaginal delivery and another for cesarean, in which a sequential analysis of the results obtained with carbetocin and oxytocin in the prevention of PPH and consequences related to the occurrence of the hemorrhagic event. The perspective used was that of the third-party payer (Colombian healthcare system); only direct medical costs were taken into account. Incremental costs and effectiveness in terms of quality-adjusted life years (QALY, obtained from the literature) were evaluated for a one-year time horizon. The costs were expressed in Colombian pesos of 2016 (1 USD = 3.051 COP). RESULTS: In the vaginal delivery model, the average cost of care for a patient receiving prophylaxis with uterotonic agents was $ 347,750 with carbetocin and $ 262,491 with oxytocin, while the QALYs were 0.9980 and 0.9979, respectively. The incremental cost-effectiveness ratio is above the cost-effectiveness threshold adopted by Colombia. In the model developed for cesarean section, the average cost of a patient receiving prophylaxis with uterotonics was $ 461,750 with carbetocin and $ 481,866 with oxytocin and the QALYs were 0.9959 and 0.9926, respectively. Carbetocin was found to be the lowest cost and most effective alternative with a savings of $ 94,887 per avoided hemorrhagic event. CONCLUSIONS: In elective cesarean delivery, carbetocin is a dominant alternative for the prevention of PPH compared to oxytocin while representing higher costs to similar effectiveness for vaginal delivery.