OBJECTIVE Free tissue transfer to the skull base provides a watertight seal to prevent CSF leakage and donor tissue tailored to the individual defect. METHODS Retrospective chart review of 38 patients who underwent free tissue transfer to the skull base between November 1995 and October 2005 at an academic, tertiary referral center. RESULTS There were 23 male and 15 female patients (average age, 58.1 years) with skull base defects resulting from oncologic resection or head trauma most frequently. Donor sites included the radial forearm (25), rectus abdominis (12), latissimus dorsi (4), anterolateral thigh, scapula, serratus anterior, and ulna (1 each). Seven patients required a second free tissue transfer indicated for flap death (3), partial flap necrosis (2), pneumocephalus (1), or tumor recurrence (1). Two patients died in the immediate postoperative period. CONCLUSIONS Free tissue transfer is a robust option in the repair of post-surgical and post-traumatic skull base defects.