Background <p>Retinopathy of prematurity (ROP) is influenced by factors, including gestational age (GA), oxygen exposure, and chorioamnionitis. However, the association between histologic chorioamnionitis (HCA) and ROP remains controversial. This study aimed to investigate the association between HCA and severe ROP.</p> Methods <p>This retrospective cohort study utilized data from the National Korean Neonatal Network registry, focusing on infants with birthweights &lt; 1500 g and GA &lt; 32 weeks. Univariate and multivariate logistic regression analyses assessed the association between HCA and severe ROP. Sub-cohort analyses were performed to evaluate the effect of HCA on severe ROP across different GA groups.</p> Results <p>Infants in the HCA cohort had lower GA and birth weights, with a higher prevalence of any-stage and severe ROP compared to those in the without-HCA cohort. However, multivariate logistic regression showed an inverse association between HCA and severe ROP. Sub-cohort analyses revealed that HCA was associated with an increased risk of severe ROP in infants born at 26–28 and 28–31 weeks, while no significant association was observed in infants born at 23–25 weeks.</p> Conclusions <p>HCA may reduce the risk of severe ROP, suggesting that intrauterine inflammation could play a protective role. Further research is needed to elucidate underlying mechanisms.</p> Impact <p><UnorderedList Mark="Bullet"> <ItemContent> <p>Retinopathy of prematurity (ROP) is influenced by numerous perinatal and postnatal factors, including low gestational age, oxygen exposure, and chorioamnionitis. However, the association between chorioamnionitis and ROP remains controversial.</p> </ItemContent> <ItemContent> <p>Our study showed that histologic chorioamnionitis (HCA) was negatively correlated with severe ROP in preterm infants, even after adjusting for confounding factors such as gestational age and birth weight.</p> </ItemContent> <ItemContent> <p>These findings suggest that HCA may have a protective effect against severe ROP, potentially mediated by inflammatory markers.</p> </ItemContent> </UnorderedList></p>