OBJECTIVE: To determine and compare the 90% effective dose (ED ) of prophylactic infusion of norepinephrine for preventing hypotension during combined spinal-epidural anesthesia for cesarean section in singleton versus twin pregnancies. METHODS: A randomized controlled trial was conducted, enrolling 200 pregnant women, 100 of which were of singleton pregnancies while the other 100 were of twin pregnancies, at West China Second University Hospital, Sichuan University between November 3, 2020 and June 2, 2021. All 200 subjects were to have Cesarean section under combined spinal-epidural anesthesia. By using a random number table, they were randomly assigned to five groups, receiving norepinephrine at the infusion dosage of 0.025, 0.050, 0.075, 0.100, and 0.125 μg/(kg·min), with 20 subjects of singleton pregnancy and 20 subjects of twin pregnancy in each group. Norepinephrine infusion started when the anesthesiologist initiated the spinal anesthetic injection and lasted until the delivery of the fetus. The primary outcome measure was the incidence of maternal hypotension during combined spinal-epidural anesthesia, up until the delivery of the fetus. Survival analysis, with survival being defined as not having hypotension, of the incidence of hypotension among the subjects was conducted. Probit regression was used to determine the ED of norepinephrine, as well as the corresponding 95% confidence interval ( ), for preventing hypotension during cesarean delivery under combined spinal-epidural anesthesia in women with singleton and twin pregnancies. RESULTS: There was no significant difference in the baseline data or the anesthesia and operation data between pregnant women of singleton pregnancy and those of twin pregnancy ( >0.05). In singleton pregnant women receiving 0.025, 0.05, 0.075, 0.1 and 0.125 μg/(kg·min) of norepinephrine, the incidence of hypotension was 50% (10/20), 35% (7/20), 20% (4/20), 10% (2/20) and 5% (1/20), respectively. The estimated ED of prophylactic norepinephrine for preventing hypotension during anesthesia was 0.100 (95% , 0.082-0.130) μg/(kg·min). In twin pregnant women receiving 0.025, 0.05, 0.075, 0.1 and 0.125 μg/(kg·min) of norepinephrine, the corresponding incidence of hypotension was 60% (12/20), 20% (4/20), 20% (4/20), 10% (2/20) and 5% (1/20). The estimated ED of norepinephrine for preventing hypotension during anesthesia was 0.098 (95% , 0.080-0.127) μg/(kg·min). Survival analysis showed significant difference in the incidence of hypotension among the five groups receiving different infusion doses in singleton pregnancy subjects, and the same is true of the twin pregnancy subjects ( <0.05). The incidence of reactive hypertension increased with increasing dosage of norepinephrine in both singleton pregnancy subjects and twin pregnancy subjects ( <0.05). There was no significant difference in the incidence of other maternal adverse reaction or in neonatal outcomes in singleton and twin pregnancy subjects receiving different dosage of norepinephrine ( >0.05). The gestational weeks, weight, and BMI were significantly different ( <0.05), while the other characteristics, including age and height, were comparable ( >0.05) between singleton and twin pregnancy subjects receiving norepinephrine at the same dosage. There was no significant difference in the incidence of hypotension, reactive hypertension, bradycardia, nausea and vomiting, and dizziness between singleton and twin pregnancy subjects receiving the same dose ( >0.05). Survival analysis displayed no significant difference in the incidence of hypotension between singleton and twin pregnancy subjects receiving norepinephrine at the same dosage ( >0.05). There was no significant difference in the ED of norepinephrine between women with singleton pregnancies and those with twin pregnancies ( >0.05). CONCLUSION: There was no significant difference in the ED of norepinephrine for preventing hypotension during combined spinal-epidural anesthesia between women with singleton pregnancy and those with twin pregnancy. Interference of other factors, including gestational age, body mass, and BMI should be considered in clinical practice.