We report cumulative results of the transsphenoidal microsurgical treatment of Cushing disease in 221 patients: 173 patients had selective adenomectomy, 25 had total hypophysectomy, 6 had partial hypophysectomy, and 12 had exploration only. Five patients were excluded from analysis because intraoperative technical difficulties precluded exposure of the pituitary gland. The selection of candidates for transsphenoidal exploration was based on endocrinologic criteria. Magnetic resonance imaging was the preferred radiologic test. Selective venous sampling of adrenocorticotropic hormone further refined the diagnosis when endocrinologic and radiologic procedures were not definitive. Remission of disease was achieved in 164 of 216 (76%) patients analyzed (95% CI, 69 to 81). Among patients with histologic confirmation of adenomas, the percentage having remission was significantly higher (P less than 0.001) in patients with microadenomas than in patients with macroadenomas and in patients with intrasellar adenomas than in patients with extrasellar extension of their adenoma or perforation of the sellar floor by adenoma (P less than 0.001). Five patients had an ectopic source of adrenocorticotropic hormone secretion. Two patients had diffuse pituitary hyperplasia. Complications occurred in 9.3% of the patients, including two deaths that were apparently unrelated to surgery (CI, 5.4 to 13). The results indicate that transsphenoidal surgery is the preferred treatment for most patients with Cushing disease.