Abstract: Objective To investigate the association between the duration of early antibiotic exposure and early outcomes in high-risk preterm infants.Methods Retrospective analysis was conducted on neonates with gestational age <32 weeks who were admitted to the neonatal intensive care unit (NICU) of the Affiliated Hospital of Xuzhou Medical University from January 2020 to June 2022, without a confirmed diagnosis of early-onset sepsis (EOS). Using the median number of days of early antibiotic exposure (7 days) as the cutoff, neonates were divided into two groups: antibiotic exposure≤7 days and >7 days. Maternal conditions, general data, antibiotic use, and in-hospital complications were compared between the two groups.Results A total of 121 preterm infants who initially had no definite infection but received early antibiotic exposure were included. Compared with the ≤7-day group, the >7-day group showed increases in the incidences of feeding intolerance (FI) and bronchopulmonary dysplasia (BPD) (P<0.05). Furthermore, there were no significant differences between the two groups in the incidences of neonatal pneumonia, patent ductus arteriosus (PDA), intraventricular hemorrhage (IVH), neonatal hyperbilirubinemia, late-onset sepsis (LOS), extrauterine growth restriction (EUGR), or mortality rate (P>0.05). Multivariate logistic regression analysis showed that early antibiotic exposure >7 days was an independent risk factor for FI (P<0.05). After controlling for confounding factors, early antibiotic exposure >7 days was not significantly associated with the occurrence of BPD (P>0.05). Dose-response analysis indicated a linear relationship between days of early antibiotic exposure and FI; as exposure days increased, the risk of FI also increased.Conclusions For high-risk preterm infants with gestational age <32 weeks and without confirmed EOS, early antibiotic exposure >7 days is an independent risk factor for feeding intolerance, and longer exposure is associated with a higher risk of feeding intolerance. However, it has no impact on BPD, LOS, IVH, or mortality outcomes.