Patent ductus arteriosus is a common problem in very low birth weight infants. Prostaglandin synthesis inhibitors such as indomethacin and ibuprofen are widely used preferred medications for ductal closure but the question of which one should be preferred is controversial. There are some studies in the literature comparing their pharmacokinetics, efficacy, side effects and long-term outcomes. In this review we aimed to focus on prostaglandin synthesis inhibitors with their pharmacodynamic and pharmacokinetic in relation to oral and intravenous forms. Oral ibuprofen seems to be an effective and cheap alternative to the intravenous forms. Studies in extremely low birth weight infants that also evaluate the neurodevelopment will clarify its use.