To analyze the clinical differences between multiple and singleton pregnancies with early-onset pre-eclampsia.The present retrospective cohort study included patients with early-onset pre-eclampsia diagnosed at a tertiary hospital in China between January 2012 and June 2014. The patients were divided into a multiple pregnancy group (MP group) and a singleton pregnancy group (SP group). Differences in maternal and fetal outcomes before and after birth were compared between the two groups.Overall, 100 patients were included (21 MP group; 79 SP group). The systolic and diastolic blood pressure values at admission were significantly lower in the MP group than in the SP group (P=0.032 and P=0.015, respectively), and the incidence of pregnancy edema was significantly higher (P=0.015). Moreover, the mean neonatal birth weight in the MP group was significantly higher than that in the SP group (P<0.001). The frequencies of abnormal umbilical arterial resistance score, abnormal fetal heart rate, low birth weight, low Apgar score, neonatal cardiovascular abnormalities, and neonatal infections were significantly lower in multiple pregnancies (P<0.05 for all).Early-onset pre-eclampsia in multiple pregnancies seems to have a protective effect on neonatal survival and improves maternal and fetal outcomes. Disease progression might be delayed when compared with early-onset pre-eclampsia in singleton pregnancies.