Cerebrospinal fluid (CSF) fistulae are problematic because of the high risk of meningitis and other infectious complications, as well as the potential for critically delaying chemotherapy in cases associated with malignancy. The plastic surgical literature suggests vascularized autologous tissue for the treatment of chronically draining CSF fistulae. Many of these patients, however, are debilitated, have multiple comorbidities, and may have a limited life expectancy, making the lengthy surgery and the associated donor-site morbidity of a regional or free tissue transfer procedure unattractive. There is a need for an alternative procedure that is a less morbid, yet equally effective solution for the obliteration of CSF fistulae. Herein we report the first use of acellular dermal matrix to successfully seal a persistent cranial CSF fistula.