Background: There is considerable literature on incidence and medical management of postsurgical chylothorax in children but little is known about outcomes of thoracic duct ligation (TDL) for patients refractory to medical therapy. Methods: A retrospective review of patients undergoing TDL after cardiothoracic surgery (1992 through 2007) was done. Data on demographics including cardiac morphology, characteristics of chylous drainage, medical management, and post-TDL course were collected. When available, imaging studies of the upper body venous drainage vessels were examined. Results: Twenty patients (median age, 0.65 years; range, 0.03 to 11 years; weight, 7.0 kg; range, 2.6 to 30 kg) had a diagnosis of chylothorax made 8.5 days (range, 2 to 118 days) after initial operation. Median duration of pre-TDL medical management was 17.5 days (range, 7 to 69 days). Median drainage for 5 days preceding TDL was 34.5 mL · kg-1 · d-1 (range, 15 to 135 mL · kg-1 · d-1) with maximal output of 65 mL · kg-1 · d-1 (range, 30 to 200 mL · kg-1 · d-1). After TDL, there was a decrease in median drainage to 13 mL · kg-1 · d-1 (range, 4 to 160 mL · kg-1 · d-1; p = 0.003). Chest tubes were removed 8.5 days (range, 4 to 34 days) after TDL. There were 4 deaths (none attributed to TDL), 2 treatment failures (post-TDL chest tube drainage > 2 mL · kg-1 · d-1 > 14 days), and 2 recurrences (after initial chylothorax resolution and hospital discharge). Three patients had documented upper body venous thrombosis. Univariate analysis demonstrated thrombosis of upper body venous vessels (p = 0.02) and prolonged post-TDL chest tube drainage (p = 0.01) were risk factors for death, treatment failure, or chylothorax recurrence. Conclusions: Thoracic duct ligation leads to a major reduction in chest tube drainage and prompt tube removal in most pediatric patients and should be considered early in refractory postoperative chylothorax. Patients with upper body venous thrombosis associated with chylothorax are at a high risk for failure of TDL and mortality.