Chylothorax is a known complication of postcardiac surgery and the most common cause of pleural effusion in neonates. Conservative management is usually adopted, including Nil‐per‐Oral (NPO), treatment of underlying etiology of infection, and use of octreotide. Chylothorax resistant to medical therapy and drainage is often treated by chemical pleurodesis. Previously used pleurodesis agents have included talc, minocycline, OK‐432, bleomycin, and povidone‐iodine. 50% Dextrose (D50) has been reported to be useful for pleurodesis in adults. We successfully managed two cases of prematurely born infants with D50 as an alternative chemical sclerosant for chemical pleurodesis in a resistant chylothorax and discussed evidence of its use in the literature