Advances in endoscopic endonasal transsphenoidal surgery have led to improved post-operative outcomes after pituitary adenoma resection, including reduced length of stay, complications and readmission rates, without compromising safety and satisfaction. Our team implemented a perioperative protocol in January 2021 for patients undergoing endoscopic, transsphenoidal pituitary surgery. This study compares pre-operative characteristics and post-operative outcomes in 279 patients between 2016 and 2022 (128 pre-protocol and 151 post-protocol). Our protocol includes interdisciplinary pre-operative evaluations, unified communication, cortisol thresholds for post-operative glucocorticoid replacement, and fluid restriction to prevent delayed hyponatremia. Median age was 54 ± 17 years with 50.8% females. There were 229 (82.1%) macroadenomas (> 1 cm) and 50 (17.9%) microadenomas/cysts (< 1 cm). Mean diameter was 18 (transverse), 18 (cranio-caudal), 16 (antero-posterior) mm. Tumor types included 125 (44.8%) gonadotroph, 46 (16.4%) adrenocorticotroph, 40 (14.3%) lactotroph, 26 (9.3%) Rathke's cysts, 19 (6.8%) somatotroph, 13 (4.6%) non-diagnostic, 3 (1%) somatotroph-lactotroph, 3 (1%) mammosomatotroph, 2 (0.71%) null cell, and 2 (0.7%) thyrotroph adenomas. Post-protocol, 74.2% of patients were discharged on POD1, compared to 46.1% pre-protocol (p<0.0001). Transient arginine vasopressin deficiency (AVD) decreased from 10.4% (pre-protocol) to 4.6% post-protocol (p=0.101). Hyponatremia occurred in 13.3% pre-protocol and 4.6% post-protocol. Emergency department visits dropped from 9.4% to 3.9%, and readmissions decreased from 7.8% to 2.6%. Persistent AVD affected 2.3% pre-protocol and 1.3% post-protocol patients. CSF leaks occurred in 8.5% pre-protocol and 7.3% post-protocol. Implementing an interdisciplinary, peri-operative protocol for transsphenoidal endoscopic pituitary surgery improves length of stay while minimizing readmissions and surgery-related complications.