OBJECT This study details the extent of resection and complications associated with endonasal endoscopic surgery for pituitary tumors invading the cavernous sinus (CS) using a moderately aggressive approach to maximize extent of resection through the medial CS wall while minimizing the risk of cranial neuropathy and blood loss. Tumor in the medial CS was aggressively pursued while tumor in the lateral CS was debulked in preparation for radiosurgery. METHODS A prospective surgical database of consecutive endonasal pituitary surgeries with verified CS invasion on intraoperative visual inspection was reviewed. The extent of resection as a whole and within the CS was assessed by an independent neuroradiologist using pre- and postoperative Knosp-Steiner (KS) categorization and volumetrics of the respective MR images. The extent of resection and clinical outcomes were compared for medial (KS 1-2) and lateral (KS 3-4) lesions. RESULTS Thirty-six consecutive patients with pituitary adenomas involving the CS who had surgery via an endonasal endoscopic approach were identified. The extent of resection was 84.6% for KS 1-2 and 66.6% for KS 3-4 (p = 0.04). The rate of gross-total resection was 53.8% for KS 1-2 and 8.7% for KS 3-4 (p = 0.0006). Six patients (16.7%) had preoperative cranial neuropathies, and all 6 had subjective improvement after surgery. Surgical complications included 2 transient postoperative cranial neuropathies (5.6%), 1 postoperative CSF leak (2.8%), 1 reoperation for mucocele (2.8%), and 1 infection (2.8%). CONCLUSIONS The endoscopic endonasal "medial-to-lateral" approach permits safe debulking of tumors in the medial and lateral CS. Although rates of gross-total resection are moderate, particularly in the lateral CS, the risk of permanent cranial neuropathy is extremely low and there is a high chance of improvement of preexisting deficits. This approach can also facilitate targeting for postoperative radiosurgery.