OBJECTIVEStereotactic radiosurgery (SRS) is used for the management of residual or recurrent Cushing’s disease (CD). Increasing experience and technological advancements of Gamma Knife radiosurgery (GKRS) systems can impact the outcomes of CD patients. The authors evaluated the association of their center’s growing experience and the era in which GKRS was performed with treatment success and adverse events in patients with CD.METHODSThe authors studied consecutive patients with CD treated with GKRS at the University of Virginia since installation of the first Gamma Knife system in March 1989 through August 2019. They compared endocrine remission and complication rates between patients treated before 2000 (early cohort) and those who were treated in 2000 and later (contemporary cohort).RESULTSOne hundred thirty-four patients with CD underwent GKRS during the study period: 55 patients (41%) comprised the early cohort, and 79 patients (59%) comprised the contemporary cohort. The contemporary cohort, compared with the early cohort, had a significantly greater treatment volume, radiation prescription dose, maximal dose to the optic chiasm, and number of isocenters, and they more often had cavernous sinus involvement. Endocrine remission rates were higher in the contemporary cohort when compared with the early cohort (82% vs 66%, respectively; p = 0.01). In a Cox regression analysis adjusted for demographic, clinical, and SRS characteristics, the contemporary GKRS cohort had a higher probability of endocrine remission than the early cohort (HR 1.987, 95% CI 1.234–3.199; p = 0.005). The tumor control rate, incidence of cranial nerve neuropathy, and new anterior pituitary deficiency were similar between the two groups.CONCLUSIONSTechnological advancements over the years and growing center experience were important factors for improved endocrine remission rates in patients with CD. Technological aspects and results of contemporary Gamma Knife systems should be considered when counseling patients, planning treatment, and reporting treatment results. Studies exploring the learning curve for GKRS are warranted.