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The aim of this study was to investigate the effects of prophylactic oral ibuprofen on the closure rate of patent ductus arteriosus (PDA).This was a retrospective study and data on infants born before 36 weeks were collected. The prophylactic group was treated with ibuprofen (10, 5, and 5 mg/kg) from days 1 to 3 after birth, respectively. The conventional group was treated with the same dose of ibuprofen from days 4 to 6 once they were echocardiographically confirmed with PDA on day 3 after birth. The placebo group was treated with 5% glucose.The closure rate of PDA in the prophylactic group significantly increased on day 7 compared with the placebo group (P = .02), but showed no difference compared with the conventional group (P = .12). Serum NT-proBNP in the prophylactic and conventional groups decreased compared with the placebo group (P = .03 vs P = .07).Prophylactic oral ibuprofen can increase the closure rate of PDA in premature infants; however, it showed no significant advantages compared with conventional treatment. Serum NT-proBNP can be used to observe PDA treatment responses in premature infants.