Background: It remains unclear which treatment approach is most advantageous for closure of patent ductus arteriosus (PDA) in preterm infants. Despite the presence of previous trials and meta-analysis, a correct and univocal strategy for closure of PDA is still under debate. Till now, standard medical treatment for PDA closure has been indomethacin/ibuprofen, percutaneous transcatheter closure, or surgical ligation. Up to date, new strategies have been reported with paracetamol. The aim of this study was to present our experience with intravenous (IV) and oral paracetamol for closing PDA in preterm neonates born before 32-week gestational age (GA). Patients and Methods: We conducted a prospective study in a neonatal intensive care unit (NICU) from a tertiary hospital in Minia University; Egypt. Eighty-seven preterm neonates born before 32-week GA with hemodynamically significant PDA (hsPDA) were enrolled. They received 15 mg/kg/6 h for 5 days IV or oral paracetamol for ductal closure. Our NICU guidelines before the current study state that only hsPDA is treated with oral ibuprofen based on the decision of the neonatologist after discussion with pediatric cardiologist. The study aims to vary the practice to use IV or oral paracetamol instead of ibuprofen to avoid side effects of nonsteroidal drugs in preterm babies. Results: During the study period, 140 babies <32 weeks admitted to the NICU assessed for eligibility to the study, 87 of them received IV or oral paracetamol for the treatment of hsPDA for a total of 5 days. Forty-five babies received IV paracetamol, while 42 received oral form with closure rate of 82.22% and 80.95%, respectively. Successful closure on paracetamol was achieved in 71 of 87 babies (81.6%). Conclusion: This study concluded that paracetamol is not only an alternative treatment in closing PDA but also may be the treatment of choice in future.