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OBJECTIVE Pituitary adenomas often invade the medial wall of the cavernous sinus (CS), but this structure is generally not surgically removed because of the risk of vascular and cranial nerve injury. The purpose of this study was to report the surgical outcomes in a large series of cases of invasive pituitary adenoma in which the medial wall of the CS was selectively removed following an anatomically based, stepwise surgical technique. METHODS The authors' institutional database was reviewed to identify cases of pituitary adenoma with isolated invasion of the medial wall, based on an intraoperative evaluation, in which patients underwent an endoscopic endonasal approach with selective resection of the medial wall of the CS. Cases with CS invasion beyond the medial wall were excluded. Patient complications, resection, and remission rates were assessed. RESULTS Fifty patients were eligible for this study, 15 (30%) with nonfunctional adenomas and 35 (70%) with functional adenomas, including 16 growth hormone-, 10 prolactin-, and 9 adrenocorticotropic hormone (ACTH)-secreting tumors. The average tumor size was 2.3 cm for nonfunctional and 1.3 cm for functional adenomas. Radiographically, 11 cases (22%) were Knosp grade 1, 23 (46%) Knosp grade 2, and 16 (32%) Knosp grade 3. Complete tumor resection, based on intraoperative impression and postoperative MRI, was achieved in all cases. The mean follow-up was 30 months (range 4-64 months) for patients with functional adenomas and 16 months (range 4-30 months) for those with nonfunctional adenomas. At last follow-up, complete biochemical remission (using current criteria) without adjuvant treatment was seen in 34 cases (97%) of functional adenoma. No imaging recurrences were seen in patients who had nonfunctional adenomas. A total of 57 medial walls were removed in 50 patients. Medial wall invasion was histologically confirmed in 93% of nonfunctional adenomas and 83% of functional adenomas. There were no deaths or internal carotid artery injuries, and the average blood loss was 378 ml. Four patients (8%) developed a new, transient cranial nerve palsy, and 2 of these patients required reoperation for blood clot evacuation and fat graft removal. There were no permanent cranial nerve palsies. CONCLUSIONS The medial wall of the CS can be removed safely and effectively, with minimal morbidity and excellent resection and remission rates. Further follow-up is needed to determine the long-term results of this anatomically based technique, which should only be performed by very experienced endonasal skull base teams.