Objective: To explore the clinical effects of ergonovine combined with hemabate on the prevention of postpartum hemorrhage and its influences on uterine involution in high-risk puerperae. Methods: A total of 200 high-risk puerperae with postpartum hemorrhage who underwent delivery in the hospital from January 2018 to October 2020 were enrolled. According to random number table method, they were divided into control group (oxytocin and ergonovine) and experimental group (hemabate on the basis of the control group), 100 cases in each group. The postpartum blood loss and bleeding rate, hemodynamic parameters, coagulation function indexes, adverse drug reactions and uterine involution were compared between the two groups. Results: The blood loss at 2 h and 24 h after delivery, complete hemostasis time, postpartum hemorrhage rate, proportion of postpartum hemoglobin decreasing not lower than 30 g/L and blood transfusion rate in experimental group were significantly lower than those in control group (P<0.05). At 1d after delivery, diastolic blood pressure (DBP) and systolic blood pressure (SBP) in experimental group were significantly lower than those in control group, while the heart rate (HR) was significantly higher than that in control group (P<0.05). There was no significant difference in the incidence of adverse drug reactions between experimental group and control group (12.00% vs 9.00%) (P>0.05). At 42 d after delivery, there were no significant differences in duration of lochia, height of uterine fundus, uterine hemorrhage rate and poor rate of uterine involution between the two groups (P>0.05). Conclusion: Ergonovine combined with hemabate can reduce postpartum blood loss, hemoglobin decrease and blood transfusion rate of high-risk puerperae, and has good effects on the prevention of postpartum hemorrhage.