Crooke cell adenoma is a very rare subtype of pituitary neoplasm that is known to be clinically aggressive. These tumors can secrete adrenocorticotropic hormone or may be endocrinologically silent. We evaluated the effect of Gamma Knife radiosurgery (GKRS) on endocrine remission and tumor control. This study comprised 5patients (2 men, 3 women; median age at GKRS, 55 years [range, 21-65 years]) with pathology-confirmed Crooke cell adenoma treated with GKRS at the Gamma Knife Center of the University of Virginia. The median time interval between transsphenoidal resection and GKRS was 5.8 months. The median margin dose was 25 Gy (range, 18-25 Gy). Median treated adenoma volume was 3.12 mL. Median follow-up was 107 months (range, 44-122 months). Tumor control was achieved in all patients. Three patients achieved endocrine remission at the last follow-up. The median time interval to cortisol normalization when off of anti-hormone secreting medication was 12 months (range, 6-24 months). Newly developed or worsening endocrinopathy occurred in 3 patients at 6, 15, and 18 months, respectively. Cranial nerve III neuropathy developed in 1 patient. Two patients required bilateral adrenalectomy at 44 months and 50 months, respectively, following GKRS. GKRS appears to be a safe and reasonably effective treatment option for Crooke cell adenoma. Multicenter studies with larger numbers of patients are needed to verify these findings.