Chylothorax is a rare but life-threatening condition in newborns, often requiring a prolonged hospital stay. To date, no unified guidance exists for best management approach. Octreotide, a somatostatin analogue, has been used to treat neonatal chylothorax due to its effect on the splanchnic circulation and lipid absorption. It is administered either subcutaneously or intravenously; for the latter, a dose range between 1 and 10 µg/kg/h is most commonly used. However, the optimal dose and way of administration remain unclear. Here, we report 2 newborn cases with large volume chylothorax (>500 mL/day), one with congenital chylothorax and one following a repair of a congenital diaphragmatic hernia (post-operative form). In both cases, a significant and sustained reduction in the volume of evacuated chyle was only seen once the dose of intravenous octreotide was increased to 20 µg/kg/h. We suggest that high-dose octreotide can be considered in seemingly refractory cases of neonatal chylothorax.