To analyze the perioperative course and clinical outcome of patients with large (lPA) and giant (gPA) pituitary adenoma who underwent endoscopic endonasal transsphenoidal surgery (EETS) using either two-dimensional (2D-E) or three-dimensional (3D-E) endoscopic systems. Single-center retrospective study of consecutive patients with lPA and gPA who underwent EETS between November 2008 and January 2023. LPA were defined as ≥ 3 cm and < 4 cm in diameter in at least one dimension and a volume of ≥ 10ccm; gPA were defined as larger than 4 cm in diameter and with a greater volume than 10ccm. Patient data (age, sex, endocrinological and ophthalmological status) and tumor data (histology, tumor volume, size, shape, cavernous sinus invasion according to the Knosp classification) were analyzed. 62 patients underwent EETS. 43 patients were treated for lPA (69.4%) and 19 patients for gPA (30.6%). 46 patients (74.2%) underwent surgical resection using 3D-E and 16 patients 2D endoscopy (25.8%). Statistical results are referred to the comparison between 3D-E and 2D-E. Patients' age ranged from 23-88 years (median 57), 16 patients were female (25.8%), 46 male (74.2%). Complete tumor resection was possible in 43.5% (27/62), partial resection in 56.5% (35/62). Resection rates did not differ between 3D-E (27 patients [43.5%]) and 2D-E (7 patients [43.8%], (p = 0.985). Visual acuity improved in 30 of 46 patients with preoperative deficit (65.2%). In the 3D-E group 21 of 32 patients (65.7%) improved, compared to 9 of 14 patients in the 2D-E group (64.3%). Improvement of visual field was achieved in 31 of 50 patients (62.0%; 22 of 37 patients in the 3D-E group [59.4%] and 9 of 13 patients in the 2D-E group [69.2%]). CSF leak was the most frequent complication and occurred in 9 patients (14.5%, [8 patients 17.4% 3D-E]) without statistical significance. Other surgical complications like postoperative bleeding, infection (meningitis) and deterioration of visual acuity and field were detected without statistical difference. New pituitary anterior lobe dysfunction was observed in 30 of 62 patients (48.4%, 8 patients [50.0%] in the 2D-E group and 22 patients [47.8%] in the 3D-E group). A transient deficit of posterior lobe was detected in 22.6% (14/62). No patient died within 30 days of surgery. Although 3D-E may improve surgical dexterity, in this series of lPA and gPA it was not associated with higher resection rates compared to 2D-E. However, 3D-E visualization during resection of large and giant PA is safe and feasible and patient's clinical outcome is not different compared to 2D-E.