Objective To present our experience with the surgical management of giant pituitary adenomas in a series of 50 cases operated on by an endoscopic endonasal approach. Methods A retrospective data analysis of all patients who underwent transsphenoidal endonasal endoscopic surgery at the General Hospital of Fortaleza, Brazil, between January 1998 and November 2011 was performed. Patients who presented with pituitary adenomas larger than 4 cm were included in the study. Analysis of factors related to the choice of the operative approach, hormonal and visual status, extent of resection, tumor control rates, clinical outcome, and complications were evaluated. Results Fifty cases (10.41%) matched our inclusion criteria. Nonfunctioning tumors were present in 42 patients (84%); among functioning adenomas, five patients (10%) had growth hormone−secreting adenomas, and three patients (6%) had prolactinomas. Total removal of the tumor occurred in 19 cases (38%), near-total removal in 9 cases (18%), and partial removal in 22 cases (44%). Postoperative cerebrospinal fluid leaks occurred in four cases (8%). Postoperative diabetes insipidus was present in 10% and new anterior pituitary insufficiency affecting one axis or more than one axis was observed in 22% and 14%, respectively. The presence of Knosp score ≥3 was associated with subtotal resection. Patients harboring hormonally active adenomas were submitted to adjuvant medical therapy for long-term clinical control. Vision improved in 38 patients (76%), with only one case of visual deterioration reported. Conclusion Transsphenoidal endoscopic endonasal surgery may provide effective treatment for patients with giant adenomas when performed by a surgical team that specializes in pituitary surgery. In cases in which total resection by the endoscopic approach may be associated with important complications, we advocate the use of partial resections followed by adjuvant drug therapy or radiotherapy. In cases of progressive enlargement of residual lesions, a second endoscopic debulking of the tumor may be considered for control of the disease.