Background The endoscopic endonasal approach for pituitary neoplasms has shown similar efficacy compared with the microscopic approach. However, outcomes and complication rates with larger macroadenomas is not as well documented. This study addresses the efficacy and outcome of the fully endoscopic endonasal approach for large and giant pituitary adenomas. Methods Endoscopic endonasal resection was performed in 39 patients with large (>3 cm) or giant (>4 cm) pituitary macroadenomas. Outcomes were assessed using formal visual examinations, endocrine status, and neurologic examinations. Statistical analyses of multiple variables were addressed for correlation to visual, endocrine, and neurologic outcomes. Results Gross total resection of the pituitary macroadenoma was achieved in 22 of 39 (56.4%) patients based on postoperative magnetic resonance imaging. Higher Knosp grade was associated with near-total resection or subtotal resection ( P = 0.0004). All patients had improved or stable visual symptoms. Time to diagnosis, preoperative visual deficit, and tumor size were not significant predictors of visual outcome. Of patients, 34 (87.1%) had a “good” endocrine outcome, whereas 5 did not. Among the 5 patients who did not have a good outcome, 1 had new hypopituitarism, and 4 required increased dosages of pharmacologic therapy. All patients with recurrent tumors had stable visual and good endocrine outcomes. Postoperative cerebrospinal fluid leak occurred in 4 patients; lumbar drainage resolved the leak in 3, and reoperation was performed in 1 patient. There were no new cranial nerve deficits, new neurologic deficits, or mortality. Conclusions Endoscopic endonasal resection of large and giant pituitary macroadenomas is safe and efficient. Postoperative complications, including cerebrospinal fluid leak, are low. Surgical efficacy of the fully endoscopic endonasal approach for large and giant macroadenomas makes the technique a preferable option in this subset of patients. [ABSTRACT FROM AUTHOR]