OBJECTIVE Congenital and acquired chylothorax presents a unique management challenge in neonates and infants. A failure of conservative therapy requires surgical ligation to prevent continued fluid and protein losses. This article examines a 15-year experience with thoracoscopic ligation of the thoracic duct. METHODS From June 1999 to December 2013, 21 patients presented with chylothorax refractory to conservative management. Sixteen patients presented following cardiac procedures, 1 after tracheoesophageal fistula repair, 1 after extracorporeal membrane oxygenation cannulation, and 1 after trauma, and 2 had congenital chylothorax. Ages ranged from 3 weeks to 5 years, and weights ranged from 2.6 to 12.7 kg. All procedures were performed in the right chest with three ports. All cases consisted of sealing of the duct at the level of the diaphragm, a mechanical pleurodesis, and fibrin glue. RESULTS All cases were completed successfully thoracoscopically. Operative time ranged from 20 to 55 minutes. There were no intraoperative complications. One patient with congenital bilateral chylothorax required a left partial pleurectomy. The chest tube duration postoperatively ranged from 4 to 14 days. Ligation failed in 2 patients, requiring a subsequent thoracoscopic pleurectomy and chemical pleurodesis, respectively. CONCLUSIONS Thoracoscopic thoracic duct ligation is a safe and effective procedure even in post-cardiac surgery patients. The site of the leak can be identified in the majority of cases, and tissue-sealing technology appears to be effective. The minimally invasive nature of the procedure has led to more expedient operative repair to avoid the morbidity associated with chyle leak.