The objective of this study was to determine the efficacy and safety of 2nd course of oral ibuprofen in closure of hemodynamically significant PDA in preterm infants after failure of the initial course. The study included 100 preterm neonates ≤ 34 weeks gestational age admitted to Kasr Al-Ainy hospital, NICU units, Cairo University between Jan. and Sept. 2009 whom had clinically significant PDA, they received initial oral ibuprofen course of 10, 5, 5 mg/kg/dose at 24h intervals. Seventy six neonates had their PDA closed after 1st course with closure rate of 76%, nineteen neonates were eligible to receive 2nd course of 20, 10, 10 mg/kg/dose at 24hr intervals. Nine of total 19 infants had their PDA closed with closure rate of 47.46%. Monitoring of urine output, renal function, hematological parameters, gastrointestinal symptoms, neurological and hepatic function showed no significant adverse effects related to treatment. Conclusion : 2nd course of ibuprofen is safe and effective in closure of PDA in preterm infants with cumulative closure rate of 89.4%.