Refractory chylothorax, a postoperative complication of CHD, is difficult to manage and sometimes fatal. Herein, we report the case of a 10-month-old infant with 22-mosaic trisomy and a coarctation complex, who developed refractory chylothorax after cardiac repairs and was successfully treated with midodrine, an oral alpha-1-adrenoreceptor agonist. Midodrine may be used as adjunctive therapy for postoperative refractory chylothorax.