Objective To examine whether a change in the approach to managing persistent patent ductus arteriosus (PDA) from early ligation to selective ligation is associated with an increased risk of abnormal neurodevelopmental outcomes. Study design In 2005, we changed our PDA treatment protocol for infants born at ≤27 6/7 weeks' gestation from an early ligation approach, with prompt PDA ligation if the ductus failed to close after indomethacin therapy (period 1: January 1999 to December 2004), to a selective ligation approach, with PDA ligation performed only if specific criteria were met (period 2: January 2005 to May 2009). All infants in both periods received prophylactic indomethacin. Multivariate analysis was used to compare the odds of a composite abnormal neurodevelopmental outcome (Bayley Mental Developmental Index or Cognitive Score <70, cerebral palsy, blindness, and/or deafness) associated with each treatment approach at age 18-36 months (n = 224). Results During period 1, 23% of the infants in follow-up failed indomethacin treatment, and all underwent surgical ligation. During period 2, 30% of infants failed indomethacin, and 66% underwent ligation after meeting prespecified criteria. Infants treated with the selective ligation strategy demonstrated fewer abnormal outcomes than those treated with the early ligation approach (OR, 0.07; P  = .046). Infants who underwent ligation before 10 days of age had an increased incidence of abnormal neurodevelopmental outcome. The significant difference in outcomes between the 2 PDA treatment strategies could be accounted for in part by the earlier age of ligation during period 1. Conclusion A selective ligation approach for PDAs that fail to close with indomethacin therapy is not associated with worse neurodevelopmental outcomes at age 18-36 months.