Background <p>Perinatal acidosis is common in preterm infants and is associated with adverse short-term outcomes. However, its role in guiding the management of patent ductus arteriosus (PDA) remains unclear. This study aimed to evaluate the PDA treatment patterns and neonatal outcomes in preterm infants with and without perinatal acidosis.</p> Methods <p>We conducted a nationwide cohort study using the Korean Neonatal Network registry. Very low birth weight infants born before 30 weeks’ gestation between 2015 and 2021 were included. Perinatal acidosis was defined as a blood pH &lt; 7.20 and a base deficit &lt; 10 mEq/L within the first hour after birth. Multivariate logistic regression was used to evaluate the association between PDA treatment and neonatal outcomes stratified by acidosis status.</p> Results <p>Among 6,158 infants, 441 (7.2%) experienced perinatal acidosis. The incidence of PDA and its treatment rates did not significantly differ between infants with and without perinatal acidosis. After adjusting for confounders, PDA treatment was associated with a significantly reduced risk of mortality, and the composite outcome of bronchopulmonary dysplasia (BPD) or death before 36 weeks’ postmenstrual age, irrespective of acidosis status. However, PDA treatment increased the risk of BPD in both groups.</p> Conclusions <p>PDA treatment was associated with improved survival but increased BPD risk in preterm infants regardless of perinatal acid-base status. Perinatal acidosis should not be considered a contraindication to PDA treatment. These findings support individualized, physiology-guided PDA management in preterm infants.</p>