Objective To assess long-term efficacy of the gasket seal, a method for watertight closure of the cranial base using autologous fascia lata held in place by a rigid buttress, in a large case series. Methods A prospectively acquired database of all endonasal endoscopic surgeries performed over a 5-year period at Weill Cornell Medical College starting in September 2005 was reviewed. Results The gasket seal was used in 46 consecutive patients. Mean age was 53 years (range 7–83 years). All patients had extensive intracranial disease with a significant intraoperative cerebrospinal fluid (CSF) leak. Pathology included craniopharyngioma (39.1%), meningioma (23.9%), and pituitary adenoma (17.4%). After a mean follow-up of 28 months (range 3–63 months), two (4.3%) patients had a postoperative CSF leak. Excluding the patients with adenomas, the CSF leak rate was 5.2% (2 of 38 patients). One leak was controlled with reoperation, and the other was stopped with a lumbar drain (LD). The significance of pathology, type of approach, exposure of the ventricular system, use of fat graft, use of nasoseptal (NS) flap, and use of lumbar drain (LD) was examined, and none of these were significant predictors of postoperative CSF leak. Conclusions Gasket seal closure is a reliable long-term effective method for achieving watertight closure of the cranial base. It can be used in association with an intracranial fat graft, NS flap, LD, and tissue sealants. In this series, none of these other factors were significant predictors of postoperative CSF leak.