Objective To compare the efficacy and safety of oral paracetamol and oral ibuprofen for the pharmacological closure of patent ductus arteriosus (PDA) in preterm infants. Study design This prospective, randomized, controlled study enrolled 90 preterm infants with gestational age ≤30 weeks, birthweight ≤1250 g, and postnatal age 48 to 96 hours who had echocardiographically confirmed significant PDA. Each enrolled patient received either oral paracetamol (15 mg/kg every 6 hours for 3 days) or oral ibuprofen (initial dose of 10 mg/kg, followed by 5 mg/kg at 24 and 48 hours). Results Spontaneous closure rate for the entire study group was 54%. After the first course of treatment, the PDA closed in 31 (77.5%) of the patients assigned to the oral ibuprofen group vs 29 (72.5%) of those enrolled in the oral paracetamol group (P = .6). The reopening rate was higher in the paracetamol group than in the ibuprofen group, but the reopening rates were not statistically different (24.1% [7 of 29] vs 16.1% [5 of 31]; P = .43). The cumulative closure rates after the second course of drugs were high in both groups. Only 2 patient (2.5%) in the paracetamol group and 3 patients (5%) in the ibuprofen group required surgical ligation. Conclusion This randomized, controlled clinical study compared oral paracetamol with ibuprofen in preterm infants and demonstrated that paracetamol may be a medical alternative in the management of PDA.