Background: Pathophysiology and treatment of ibuprofen in the mechanism of ductal closure full-term remain unclear. Objective: Assessing the role of prostaglandins, VEGF, IPF and the effect of oral ibuprofen in the mechanism of ductus arteriosus (DA) closure. Method: This study conducted at three hospitals in Denpasar, Bali from March to October 2015. First design, a cross-sectional design was conducted in patients with and without PDA aged ≥ 48 h to know the role of PGE2, VEGF and IPF. Second, a double-blind randomized controlled trial design in patients with PDA to determine the effect of ibuprofen in ductal closure. Patients with PDA were randomized to have placebo or oral ibuprofen with consecutive dose of 10-5-5 mg/kg/day. All consecutive subjects performed echocardiography, PGE2, VEGF and IPF examination on the first and fourth day. Results: The mean level of PGE2 was higher in the group with PDA than non-PDA group, while there was no difference in the mean level of VEGF and IPF. Oral ibuprofen showed no effect in reducing DA diameter. There was a moderate positive association between mean differences of PGE2 and ductal diameter after treatment. No events of oliguria, NEC and IVH were recorded in both groups. Conclusion: A high level of PGE2 appears to play a pivotal role in DA patency of fullterm neonates. Administration of oral ibuprofen in 10-5-5 mg/kg schedule could not induce PDA closure in full-term neonates.