Although transsphenoidal adenomectomy is the first treatment choice for Cushing's disease (CD), tumor recurrence rates are as high as 45%, resulting in a therapeutic challenge for endocrinologists and neurosurgeons. For recurrent/persistent CD (RCD/PCD), Repeat transsphenoidal surgery (RTSS), radiotherapy, gamma knife radiosurgery (GKRS) or bilateral adrenalectomy may be considered. The purpose of the study was to report the treatments and outcomes of RCD/PCD in a single center. A retrospective study was performed on 55 RCD/PCD patients from a single center between 2000 and 2012 at Peking Union Medical College Hospital (PUMCH). Among the 55 RCD/PCD patients, 43 achieved remission (78%), and 11 maintained a PCD status (20%). The average times to recurrence after the initial treatment and Repeated treatment were 43.25±10.3 and 5.13±4.7 months, respectively (P=0.006); 17.6% of the patients experienced recurrence within the first year, and 52.9% of the patients experienced recurrence within 1.1-5.0 years. For the Repeated treatments, surgery was more effective for the biochemical remission of serum cortisol and adrenocorticotrophic hormone (ACTH) levels than radiotherapy. Delayed remission occurred in 28.9% (11/38) of the patients after Repeated surgery. Considering the previous biochemical levels after the initial surgery in RCD patients, 19.75% of patients experienced recurrence when serum cortisol levels were less than <3 µg/dL, and 51.4% of patients experienced recurrence under conditions of hypocortisolism and when 24-hour urinary free cortisol (24 UFC) was undetectable. RTSS remains a recommended treatment option for RCD/PCD patients while radiotherapy is suggested as an adjunctive treatment. Intensive follow-up is recommended, as patients with serum cortisol levels <3 µg/dL or undetectable 24 UFC levels can still experience recurrence after surgical treatment.