Very low-birth-weight premature infants (VLBWs) are fed via nasal or oro-gastric tube for a long time because of the physiological inability to coordinate swallowing, sucking, and breathing until at least 34 weeks of gestational age. Both bolus and continuous feeding modes are widely described in the literature; both modes have specific risks and benefits, and there is no evidence in the literature as to which mode is best in terms of tolerance and adverse effects. To date, the characteristics of enteral feeding that are associated with better feeding tolerance and fewer adverse effects have not been uniquely documented. There are currently no data in the literature directly comparing different modes of enteral feeding tube management in the preterm VLBW infant. Therefore, our study aims to evaluate different modes of enteral feeding tube management (extemporaneous vs. permanent introduction/removal and oral vs. nasal introduction route) in order to optimize enteral feeding management of the VLBW infant.