Background Patent ductus arteriosus (PDA) is common in very premature infants. Pharmacological closure of PDA with indomethacin, a prostaglandin inhibitor, has remained the mainstay of treatment in premature infants over the last three decades. Intravenous ibuprofen was recently shown to be as effective and to have fewer adverse reaction in preterm infants. If equally effective, then oral ibuprofen for PDA closure would have several important advantages over the intravenous route. This study was designed to assess the efficacy and safety of oral ibuprofen and intravenous ibuprofen for the early pharmacological treatment of PDA in LBW preterm infants with respiratory distress syndrome. Methods A randomized, single-blinded, controlled study was performed on premature neonates at the neonatal care unit of the University Hospital for Obstetrics and Gynecology”Koco Gliozheni”, Tirana, Albania, from January 2010 to December 2012. The study enrolled 68 preterm infants with gestational age between 28-32 weeks, birth weight ≤ 2000 g, postnatal age 48-96 h, and had echocardiographically confirmed significant PDA. The preterm infants received either intravenous or oral ibuprofen randomly as an initial dose of 10 mg/kg, followed by 5 mg/kg at 24 and 48 h. After the first dose of treatment in both groups, echocardiographic evaluation was performed, to determine the need for a second or third dose. The rate of ductal closure, adverse effects, complications, and the patient’s clinical course were recorded. Results All patients were born after 28 until 32 weeks’ gestation. 36 patients were treated with oral ibuprofen and 32 with intravenous ibuprofen in this period. After the first course of the treatment, the PDA closed in 30 (83.3%) of the patients assigned to the oral ibuprofen group versus 23 (71.8%) of those enrolled in the intravenous ibuprofen group (p = 0.355). There was no difference between treatment groups in demographics or baseline renal function. In the evaluation of renal tolerance, none of the patients had oliguria. There were no significant differences with respect to complications during the stay. Conclusions In low birth weight infants, the rate of early ductal closure with oral ibuprofen is at least as good as with the intravenous route. Oral ibuprofen is associated with fewer adverse effects, Alketa Hoxha, Ermira Kola, Numila Kuneshka, Eduard Tushe, and Literatura