The efficacy of endoscopic transsphenoidal surgery (ETS) for Cushing disease has not been clearly established. To assess efficacy of a pure endoscopic approach for treatment of Cushing disease and determine predictors of remission. A prospectively acquired database of 61 patients undergoing ETS was reviewed. Remission was defined as postoperative morning serum cortisol of <5 μg/dL or normal or decreased 24-hour urine-free cortisol level in follow-up. Overall, hypercortisolemia resolved in 58 of 61 patients (95%) by discharge. Tumor size did not predict resolution of hypercortisolemia at discharge (microadenomas [97%], magnetic resonance imaging-negative Cushing [100%], macroadenomas [87%]). At 2- to 3-month evaluations, 45 of 49 patients (91.8%) were in remission. Fifty patients were followed for at least 12 months (mean, 28 months; range, 12-72). Forty-two (84%) achieved remission from a single ETS. In these patients, there was no significant difference in remission rates between microadenomas (93%), magnetic resonance imaging-negative (70%), and macroadenomas (77%). Patients with history of previous surgery (n = 14, 23%) were 9 times less likely to achieve follow-up remission (P = .021). In-house cortisol level of <5.7 μg/dL provided the best prediction of follow-up remission (sensitivity 88.6%, specificity 83.3%). Postoperative diabetes insipidus occurred transiently in 7 patients (9%) and permanently in 3 (5%). One patient experienced postoperative cerebrospinal fluid leak that resolved with further surgery. ETS for Cushing disease provides high rates of remission with low rates of complications regardless of size. Although patients with a history of previous surgery are less likely to achieve remission, the majority can still achieve remission following treatment.