OBJECTIVES: Intravenous Indomethacin and Ibuprofen are treatment of choice for pharmacologic closure of patent ductus arteriosus (PDA) in preterm infants according to inhibitory effect on cyclooxygenase. However, unavailability of the intravenous formulations in many countries leads to off-label use of oral NSAIDs for PDA closure. This study therefore aimed to determine the effectiveness and safety of oral NSAIDs compared to their intravenous formulations for PDA closure in preterm and/or low birth weight infants. METHODS: Randomized or quasi-randomized (RCTs) and observational studies comparing oral NSAIDs to intravenous Indomethacin or Ibuprofen with reported result of closure rate were identified. Fixed and random effect models were used for meta-analyses. Heterogeneity test including I were performed to assess the appropriateness of pooling the data. RESULTS: Fourteen studies comparing the effectiveness and safety of oral NSAIDs (Indomethacin, Ibuprofen and Sulindac) with intravenous NSAIDs (Indomethacin and Ibuprofen) were recruited. For the primary outcome (closure rate), no statistically significant difference between oral Ibuprofen and intravenous NSAIDs group [five RCTs of oral Ibuprofen versus Intravenous Ibuprofen group; RR = 1.12 (95% CI 0.990, 1.240, I CONCLUSIONS: No statistically significant difference in the effectiveness of oral Ibuprofen and oral Indomethacin compared to the intravenous NSAIDs with similar adverse outcome were observed. Oral formulations of Indomethacin and Ibuprofen might be considered as an alternative pharmacologic closure in PDA treatment for the NICU settings where intravenous NSAIDs is unavailable.