Thoracic duct injury is a rare but serious complication following surgery of the neck or chest that leads to uncontrolled chyle leak. Conventional management includes drainage, nutritional modification, or aggressive surgical interventions such as thoracic duct ligation, flap coverage, fibrin glue, or talc pleurodesis; few successful medical therapeutics are available. We report a case of a high-output chylothorax refractory to aggressive medical and surgical interventions. Chyle output decreased substantially after initiating midodrine, an α1-adrenergic agonist that causes vasoconstriction of the lymph system, reducing chyle flow. This case report suggests that midodrine may be a novel therapeutic for refractory chyle leaks.