To study the association between technique for definitive closure of PDA and peri-procedural opioid utilization in preterm neonates. A retrospective cohort study comprising all premature neonates and infants with a PDA who underwent surgical ligation (SL) between February 2020 and December 2022 or transcatheter PDA closure (TCPC) between August 2020 and February 2023. Intra-procedural and post-procedural opioid use was systematically quantified and compared between the two groups before and after 1:1 propensity score matching. We hypothesized that preterm neonates and infants undergoing TCPC will have an overall reduction in peri-procedural opioid exposure compared to those undergoing SL. The study included 52 preterm infants in the SL group and 74 in the TCPC group. After propensity score matching, infants undergoing TCPC received significantly lower intra-procedural (4.33 vs 5.99 µg/kg, P = 0.037) and post-procedural (0.09 vs 0.32 mg/kg, P < 0.001) opioids. A significantly lower proportion of infants undergoing TCPC were exposed to post-procedural opioids (60.8% vs 92.3%, P = < 0.001). In a multivariable logistic regression model, surgical ligation was associated with sevenfold higher odds of post-procedural opioid exposure compared to TCPC (OR 7.2, 95% CI of 2.1-24.2, P = 0.001). Transcatheter PDA device closure is associated with significantly lower neonatal opioid exposure.