Introduction: Patent ductus arteriosus (PDA) is one of the most common cardiovascular problems that occur in preterminfants. This trial aimed to investigate whether acetaminophen is non-inferior to ibuprofen in closing PDA in very preterm infants.Patients and Methods: A randomized non-inferiority trial was conducted on preterm infants with a gestational age <32weeks, birth weight <1500 g, postnatal age <72 h, and PDA size >1.5 mm. Infants were randomly assigned to receive either intravenous acetaminophen (n=52) or rectal ibuprofen (n=52). The primary study outcome was the ductus closurewithin 24 hours after completion of the first and/or second course of pharmacological treatment.Results: The incidence of PDA closure after completion of the first and/or second course of pharmacological treatmentwas identical 81% (42/52). After the first course of treatment, PDA closed in 37 infants (71%) in the ibuprofen groupand 41 patients (79%) in the acetaminophen group (p>0.05). The median age (IQR) at the time of ductus closure wasalso the same in both groups, 5 (5-6) days. There were no statistically significant differences between the groups in theincidence of severe complications associated with preterm birth and mortality (p>0.05). No side effects related to pharmacological treatment were detected.Conclusions: Acetaminophen is non-inferior to ibuprofen for the closure of PDA in very preterm infants.