Objective: To determine the association between the degree of intrauterine growth restriction (IUGR) [defined by birth weight (BW) Z-score] and the efficacy of pharmacologic patent ductus arteriosus (PDA) closure and the rate of surgical PDA ligation in preterm neonates. Materials and methods: In this retrospective cohort study, we included neonates born below 30 weeks’ gestational age (GA), who received medical treatment for PDA between January 2010 and December 2018. Birth weight Z-scores were calculated using Olsen nomograms and classified into three categories: above −0.5; from −0.5 to −2.0; below−2. We compared responses to PDA treatment with non-steroidal anti-inflammatory drugs (NSAIDs) and PDA ligations between these groups utilizing multivariable logistic regression analysis. Results: Of 769 neonates with PDA, 517 (67.2%) neonates received medical treatment for PDA. Of which, 323 (62.5%) had BW Z-score above −0.5, 154 (29.8%) had from −0.5 to −2.0., and 40 (7.7%) had below −2. The efficacy of the first course of NSAIDs for the PDA closure was not different among the three groups (51% vs 49% vs 50%). Multivariable logistic regression analysis showed there was no significant difference in PDA closure rate following the first course of NSAIDs between neonates with BW Z-score below −2 and those with BW Z-score above −0.5 [adjusted odds ratio (aOR): 0.68; 95% CI: 0.33–1.39] as well as those with BW Z-score from −0.5 to −2.0 (aOR: 0.89; 95% CI: 0.59–1.35). However, the odds of PDA ligation were significantly higher among neonates with BW Z-scores below −2 (aOR: 2.67, 95% CI: 1.12–6.34) but not among neonates with Z-scores from −0.5 to −2.0 (aOR: 1.41; 95% CI: 0.84–2.39), as compared to those with BW Z-scores above –0.5. Conclusion: We observed a similar rate of PDA closure following the first course of NSAIDs between appropriately grown and growth-restricted neonates. However, severe growth restriction (BW Z-score below −2) is associated with higher rates of PDA ligation as compared to normally grown infants.