Abstract: OBJECTIVE To explore the effect of prenatal prophylactic use of antibiotics on puerperal infection and neonatal scores of the high-risk puerpera. METHODS A total of 296 high-risk puerpera who gave birth in obstetrics and gynecology department of Shengjing Hospital Affiliated to China Medical University from Jan 2019 to Jan 2022 were recruited as the research subjects and were randomly divided into the study group and the control group, with 148 cases in each group. The study group was treated with intravenous injection of cefazolin 30 min before the labor, while the control group was treated with intravenous injection of cefazolin after the labor. The status of labor, infection-related indexes, adverse reactions and neonatal status were observed and compared between the two groups of puerpera. RESULTS There were no significant differences in the high risk factors between the two groups. The more than 35 years of age, gestational hypertension and malposition were the major high risk factors. The blood loss volume at the labor and 24 hours after the labor were less in the study group than in the control group, and the length of hospital stay of the study group was shorter than that of the control group (P＜0.05). The incidence of complications was 6.1%(9/148) in the study group, 8.1%(12/148) in the control group, and there was no significant difference (χ²=0.461,P=0.497). The levels of white blood cell and neutrophils of the study group were lower than those of the control group(P＜0.05). The incidence of adverse reactions of the study group was 6.08%(9/148), lower than 16.22%(24/148) of the control group (P＜0.05). The common adverse reactions included gastrointestinal tract reactions and rash; the incidence of mild asphyxia of neonates of the study group was lower than that of the control group (P＜0.05), and the 1 min and 5 min Apgar scores of neonates were improved more significantly in the study group than in the control group(P＜0.05). CONCLUSION The prophylactic use of antibiotics may reduce the infection-related indexes of the high-risk puerpera during the puerperal state, shorten the length of hospital stay, and improve the neonatal scores; the incidence of adverse reactions is low. It is worthy to be promoted in the hospital.