Objective To determine the dose of phenylephrine through intravenous bolus to prevent hypotension in 90% of pregnant women during cesarean delivery under combined spinal and epidural anesthesia by the sequential analysis method. Methods This was a prospective, double‑blinded, and sequential study. A total of 40 pregnant women who were scheduled for cesarean delivery were enrolled and the Biased Coin up‑down method was used. The women were injected into the subarachnoid space with 0.75% of ropivacaine (10.5 mg) and fentanyl (10 µg), in addition to epidural injection of 2% lidocaine (5 ml). The effects of different doses of phenylephrine on the women were observed. The primary outcome was the dose of phenylephrine to maintain the systolic blood pressure (SBP) above 80% of the baseline before delivery. The secondary outcomes included dizziness, breathlessness, nausea, vomiting, bradycardia, rescue use of atropine and phenylephrine, secondary hypertension, the total dose of phenylephrine, the highest plane of sensory nerve block, the results of umbilical arterial and venous blood gas analysis, and 1‑min and 5‑min Apgar scores. The 90% effective dose (ED90) and 95% confidence intervals (CI) were estimated using the isotonic regression methods. Results The ED90 of phenylephrine through intravenous bolus to prevent hypotension in pregnant women under combined spinal and epidural anesthesia was 116.5 µg (95%CI 114.44‒135.33 µg). The incidence of maternal hypotension was 15%, with low incidences of hypotension related adverse reactions. The data about blood gas analysis of the neonatal umbilical vein and artery were normal, while 1 min and 5 min Apgar scores were both 10 (10, 10). Conclusions A single intravenous bolus of phenylephrine at 120 µg can effectively prevent hypotension after combined spinal and epidural anesthesia, with good neonatal outcomes.