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Objective: Transsphenoidal surgery (TSS) presents the treatment of choice for Cushing's disease (CD). Remission and recurrence rates vary dependent on tumor size, extension, adenoma visibility on magnetic resonance imaging, and neurosurgical expertise. Other than published from single-surgeon neurosurgical series so far, we have aimed to describe long-term remission and recurrence rates of CD in a series incorporating different neurosurgeons, trying to reflect care reality in the Munich Metropolitan Region, which is accommodated by three tertiary university and multiple, smaller neurosurgical centers. Design: We conducted a retrospective analysis of 120 patients who underwent first and 36 patients who underwent second TSS as treatment for CD between 1990 and 2012. Methods: Patients were divided into three groups according to remission status. Potential risk factors for recurrence, pituitary function, and strategy in persistent disease were assessed. Results: Three outcome groups were identified according to remission status after first TSS (mean follow-up 79 months): remission, 71% (85/120), disease persistence, 29% (35/120), and disease recurrence, 34% (29/85) (mean time to recurrence 54 months). After second TSS (n = 36, mean follow-up 62 months), we documented remission in 42% (15/36), disease persistence in 58% (21/36), and disease recurrence in 40% (6/15) (mean time to recurrence 42 months). Postoperative hypocortisolism after first, though not after second, TSS was associated with a lower risk of suffering disease recurrence (risk=0.72; 95% CI 0.60-0.88; exact significance (two-sided) P=0.035). Conclusions: Our study shows higher recurrence rates of CD after first TSS than previously reported. Second TSS leads an additional 8% of the patients to long-term CD remission. [ABSTRACT FROM AUTHOR]