OBJECTIVE: To estimate cost-effectiveness of carbetocine compared to oxytocin in preventing uterine atony in patients with risk factors. METHODS: A randomized pragmatic clinical trial in patients with risk factors for uterine atony was performed in the Instituto Mexicano del Seguro Social (IMSS) in Mexico City. Two therapies were included: carbeteocine and oxytocin. One hundred patients with fetal macrosomia, polyhydramnios, low insertion of the placenta, multiple gestation, prolonged labor, uterine myomas and chorioamnionitis were included in each group. The effectiveness was defined as the reduction of the number of patients with uterine atony. The use of resources was obtained from the clinical trial and the costs were gotten from financial information from IMSS, and are expressed in US 2006 dollars. Univariate and probabilistic sensitivity analyses were performed using Monte Carlo simulation. RESULTS: No statistically significant difference was found in general characteristics, obstetric background and risk factors distribution in both groups. Uterine atony was reported in 20% in the oxytocin group compared to 5% in the carbetocine one (p<0.0001). Multiple gestation and fetal macrosomia were the most frequent diagnosis, 30% (p<0.0001). Bleeding was less than 500 mL in the carbetocine group and 500 to 1000 mL in the oxytocin one (p<0.0001). Mean cost per patient treated with carbetocine was $3468 vs. $4082 for oxytocine (p<0.0001). Mean cost-effectiveness ratio for oxytocin was $5103, while for carbetocine $3651; ICER showed that carbetocine was dominant. Univariate analysis supported those results. A Monte Carlo microsimulation with 10,000 iterations was performed using probability distribution data from the clinical trial. The acceptability curve and health net benefits showed that carbetocine group was superior independently of WTP. CI 99% by ellipse method showed that carbetocine was dominant in 100% of cases. CONCLUSIONS: Carbetocine was the most cost-effective drug to prevent uterine atony in patients with risk factors.