Abstract. The objective of this study was to present the long-term results of total adrenalectomy for Cushings disease. Forty-four patients undergoing total adrenalectomy for Cushings disease between 1953 and 1989 at Leiden University Medical Center, The Netherlands, were studied retrospectively. Remission was achieved in 42 patients (95%), with a mean duration of 19 years. Adrenal remnants were observed in 12 patients (27%), and were without clinical consequence in the majority of patients, but caused early recurrent disease in 2 patients. Nine patients (20%) experienced Addisonian crises up to 30 years following treatment. Nelsons syndrome developed in 10 patients (23%) 724 years following total adrenalectomy. Prior pituitary irradiation was a protective factor against Nelsons syndrome as it delayed its onset (p= 0.025). On the other hand, subnormal dose or noncontinuous glucocorticoid replacement therapy was associated with increased risk of development of Nelsons syndrome (p= 0.047). The incidence of Nelsons syndrome increased with prolonged follow-up, and female patients seemed to be at increased risk. Quality-of-life assessment showed less favorable scores on mental health and health perception scales, for which no explanation can be found except the long-lasting metabolic effects of Cushings disease, even when successfully treated. In conclusion, total adrenalectomy remains the final treatment for Cushings disease. The presence of adrenal remnants which can cause recurrent disease and the development of Nelsons syndrome during prolonged follow-up enhance the need for continued regular follow-up. Pituitary irradiation prior to total adrenalectomy delays the onset of Nelsons syndrome.