Objective To study the surgical treatment of adrenocorticotropic hormone independent macronodular adrenal hyperplasia (AIMAH).Methods The clinical data of 12 AIMAH patients were analyzed retrospectively.There were 3 males and 9 females, with an average age of 55 years (range, 39-67 years).10 cases had typical clinical features of Cushing syndrome.Endogenous hypercortisolism was confirmed on the basis of loss of circadian rhythm of serum cortisol, high late-night serum cortisol level and inadequate cortisol suppression after overnight low-dose dexamethasone suppression test.ACTH independence was established on the basis of suppressed serum ACTH levels and inadequate cortisol suppression after overnight high-dose dexamethasone suppression test.CT scan showed bilateral enlargement of the adrenal glands with multiple macronodules.Steroid supplement was given after operation.Results Surgical intervention was performed in all the patients.Seven patients underwent bilateral adrenalectomy,and unilateral adrenalectomy was performed in 5 patients, one of whom had the history of contralateral adrenalectomy.Pathological examination confirmed multinodular hyperplastic adrenal enlargement.The average duration of postoperative follow-up was 50 months (range, 1-105 months).One patient undergoing bilateral adrenalectomy died from respiratory failure and pulmonary infection one month after operation.Remission of Cushing syndrome symptoms was obtained after surgery in other 11 patients.For these 11 cases,the serum cortisol declined into normal ranges, but suppressed serum ACTH levels and inadequate cortisol suppression after overnight low-dose dexamethasone suppression test were still present.Two patients received contralateral adrenalectomy due to recurrent overt Cushing syndrome after one year and 5 years, respectively.Conclusions Unilateral adrenalectomy might be an effective and safe treatment modality for AIMAH, but subclinical hypercortisolism would be present postoperatively.Contralateral adrenalectomy may be performed in case of the recurrence of overt Cushing syndrome.