Obliteration of the sphenoid sinus using fat is often used after transsphenoidal hypophysectomy. The morbidity of this approach includes donor site complications, fat necrosis, and delayed mucocele formation. As obliteration with fat is intended to prevent cerebrospinal fluid (CSF) leakage, an alternative for this technique would be techniques used for CSF rhinorrhea repair. Instead of sinus obliteration, these defects are repaired with fascial autografts, which are unfortunately associated with donor site complications. To avoid sinus obliteration and donor site complications, we have reconstructed the sella with acellular dermal allograft in lieu of sinus obliteration. Transsphenoidal hypophysectomy was performed under combined microscopic and endoscopic visualization. For closure, the sellar anterior wall was reconstructed with acellular dermal allograft, septal cartilage/bone autograft, and fibrin glue. The sinus mucosa was then draped over the reconstruction and held in place with microfibrillar collagen hemostat slurry. The sphenoid sinus was not obliterated. Postoperatively, all patients underwent serial nasal endoscopy. Thirteen patients underwent the procedure as described for removal of pituitary adenoma. Postoperative discomfort and pain were minimal. Intraoperative CSF leaks were identified in five patients; none of these patients experienced a postoperative CSF leak. The microfibrillar collagen hemostat was cleared by sphenoid mucociliary clearance. One patient developed acute sphenoid sinusitis several weeks after surgery; this patient did not develop meningitis. One postoperative CSF leak occurred in an obese patient, in whom an intraoperative CSF leak was not identified; this leak resolved with bedrest and delayed lumbar drainage alone. Sellar reconstruction with acellular dermal allograft may eliminate the need for sphenoid sinus obliteration after transsphenoidal hypophysectomy. Acellular dermal allograft sellar reconstruction ultimately provides for an aerated, functioning sphenoid sinus without increased CSF leak risk or potential donor site morbidity.