Background: To evaluate the efficacy and safety of carbetocin compared with oxytocin for prevention of postpartum hemorrhage (PPH) after elective cesarean section in Chinese high risk women. Methods: This was a single-center, prospective, randomized, open-label, controlled trial recruiting 852 pregnant women with one or more PPH risk factors between April 2017 and August 2019. Pregnant woman who was scheduled for an elective cesarean section were randomly assigned to receive carbetocin or oxytocin for prevention of PPH. The primary efficacy endpoint was the proportion of additional uterotonics. Results: A total of 852 pregnant women were randomly assigned to receive carbetocin (n = 442) or oxytocin (n = 410). The baseline characteristics were comparable between the two groups. The carbetocin group had lower proportion of requiring additional uterotonics (18.4% vs. 24.4%, p = 0.03 in full analysis set [FAS] analysis) to the oxytocin group. The amount of blood loss (intrapartum or postpartum) was no statistically significant difference (all p > 0.05). There were no significant differences in the postpartum hemoglobin, rate of hemostatics, blood transfusion, additional surgical interventions or uterine massage between the two groups. The rates of mild asphyxia in carbetocin and oxytocin groups were 2.1% and 1.3%, respectively. No other poor maternal and neonatal outcomes were observed in two groups. Conclusions: Carbetocin required lower rate of additional uterotonics than oxytocin for prevention of PPH after elective cesarean section in Chinese high risk women. Carbetocin was comparable to oxytocin in postpartum blood loss, postpartum hemoglobin, hemostatics, blood transfusion, additional surgical interventions or uterine massage.