The influence of somatostatin/octreotide treatment on outcomes of neonates with congenital chylothorax remains controversial. We retrospectively reviewed our experience with somatostatin/octreotide therapy in neonates with this very rare disease.Fourteen neonates with congenital chylothorax who were treated with somatostatin (3.5–7 μg/kg/h, before 2016) or octreotide (1–6 μg/kg/h, after January 2016), along with traditional management between 2013 and 2016, were retrospectively reviewed in this observational study. Their daily volumes of pleural drainage and parameters of respiratory support were recorded, and the potential side effects of somatostatin/octreotide were screened.Four patients (28.6%) had a unilateral presentation of pleural effusion, whereas 10 patients (71.4%) had a bilateral presentation. Twelve patients (85.7%) survived until discharge without later recurrence or death, whereas 2 patients (14.3%) died within the first 3 days after birth. Somatostatin/octreotide treatment was maintained for a median period of 6 days (range 1–16 days). The chest tube was removed after a median duration of 14 days (range 2–51 days), and no patient needed pleurodesis or thoracic duct ligation surgery. The average daily drain output within 3 days post-treatment (median 62 mL, range 10–651 mL) was significantly lower than that before treatment (median 133 mL, range 70–620 mL) (P = .002). The need for ventilation support was reduced in most patients (85.7%) after the initiation of somatostatin/octreotide therapy. No serious side effects were identified.Somatostatin/octreotide treatment reduced pleural drainage and respiratory support without significant side effects. Further randomized controlled studies with more patients are necessary to ascertain the benefits of somatostatin/octreotide in neonates with congenital chylothorax.