Purpose: This study aimed at evaluating the efficacy of prophylactic intravenous ibuprofen plus caffeine compared to the symptomatic management of the moderate-to-large patent ductus arteriosus ( PDA) in preterm infants. Materials and Methods: The data of 55 preterm infants with birth weight of 1,250 g and gestational ages of 32 weeks was analyzed in NICU of Kyung Hee University Hospital at Gangdong during 2013-2017. 20 to the prophylaxis ( PT) group and 35 to the symptomatic treatment (ST) group. The PT group received intravenous (IV) ibuprofen (10 mg/kg) with loading dose of caffeine citrate (20 mg/kg) within 6 h after birth, whereas the ST group started IV ibuprofen treatment if echocardiography examination verified hemodynamically significant PDA. The initial IV ibuprofen was followed by 5 mg/kg after 24 h and 48 h until PDA closure but not longer than 9 days. Echocardiography was performed before treatment and 24 hours after each dose. The rate of ductal closure, the need for ventilator care, side effects, and the infants’ clinical courses were recorded. Results: In the PT group, ductal closure was achieved in all newborns except 1. No infant required surgical ligation of the ductus and reopening of the ductus did not occurred once the closure had achieved. Among 20 of the PT group, 16 newborns (80%) were treated with 1 dose of ibuprofen, 1 (5%) with 2 doses, 1 (5%) with 3 doses, and the remaining 2 were treated with 6 and 9 doses respectively. Necrotizing enterocolitis (NEC) (≥ stage 2), intraventricular hemorrhage (IVH) grade 3-4, bleeding events, and mortality did not occurred in the PT group but it was not statistically significant. Compared to the ST group, preterm infants in the PT group were more likely to have a fewer duration of ventilator care (3.6 ± 7.5 vs. 10.6 ± 10.0 days, P = 0.01), central venous catheter (17.2 ± 5.5 vs. 39.3 ± 16.4 days, P 0.001), and earlier postnatal age of achieving feeding of 50 and 100 mL/kg/d ( P 0.001). There was no significant difference with respect to other adverse effects or morbidities. Conclusion: Ibuprofen prophylaxis in preterm infants does not reduce the frequency of morbidity of bronchopulmonary dysplasia, NEC, IVH, but does decrease the occurrence of PDA and reduce duration of ventilator care and central venous catheter usage.