Endoscopy in combination with extended approaches allow for resection of large pituitary adenomas via a transsphenoidal route. The objective of the current study was to determine a volumetric threshold for lesions with high perioperative morbidity and high rate of subtotal resection following endonasal endoscopic surgery. Thus, we analyzed a prospectively collected database of 71 patients who underwent endoscopic transsphenoidal approaches for macroadenomas (diameter >1 cm). Extend of resection (EOR) was calculated based on volumetric analysis of pre-and post-operative contrast-enhanced MRI. Average EOR was 97.8% and a gross total resection (GTR) was achieved in 76.1% of all patients. GTR was accomplished in 92.0% versus 38.1% of adenomas either without or with CS invasion, respectively. Likewise, GTR was accomplished in 90.2% versus 40.0% of lesions less than or greater then 10 cm(3) respectively. However, even if only subtotal resection was achieved, 90.3% of tumor volume was removed. At 17 months follow-up, visual field defects improved in 80.8% of patients. Complications included permanent diabetes insipidus (5 patients), panhypopituitarism (4 patients), injury to the ophthalmic artery (1 patient) and CSF leak (1 patient). On multivariate logistic regression, two factors negatively predicted GTR: invasion of the CS and volume greater than 10 cm(3). A 10 cm(3) threshold was a stronger predictor of EOR and complication risk than diameter-based measurements. A volume greater than 10 cm(3) and CS invasion may help to identify pituitary lesions associated with a higher likelihood of subtotal resection and post-operative morbidity.