Abstract: Objective: To evaluate the clinical value of patients with adrenocorticotropic hormone-independent macronodular adrenal hyperplasia(AIMAH) after unilateral adrenalectomy in order to explore the feasibility of this method as the first choice for the treatment of AIMAH.Methods: The clinical data of 46 patients with AIMAH after unilateral adrenalectomy from 2008 to 2019 were analyzed retrospectively. There were 20 males and 26 females, with an average age of(55.13±8.89) years. There were 6 cases of subclinical type, 33 cases of clinical type and 7 cases of high-risk type. All patients had different clinical features before surgery, 41 patients with hypertension, 27 patients with overweight or obesity, 20 patients with increasing blood cortisol concentration at 8 am, 42 patients with increasing 24-hour urinary free cortisol. Failed to suppress cortisol secretion was observed in all 41 patients conducted with 2 mg dexamethasone suppression tests and in all 40 patients conducted with 8 mg dexamethasone suppression tests. On CT images, bilateral adrenal glands were obviously enlarged with multiple unequal sized nodules. Forty-six patients underwent unilateral adrenalectomy. The patients were discharged from hospital after operation. They were asked to follow up at 1, 3, 6, 9 and 12 months after surgery and thereafter every six months. Statistical analysis was performed using SPSS 23.0 software, and GraphPad Prism 8 was used for drawing.Results: The resected specimen showed multiple nodules of various sizes, and the section was golden yellow. A total of 42 people were followed up, with an average follow-up of 26.93 months, and 4 were lost to follow-up. During the follow-up period, 29 patients did not recur and 13 patients recurred. The patients without recurrence had Cushing's symptoms improved, blood pressure decreased. The mean systolic blood pressure decreased by 22.30 mmHg(P=0.001), and the mean diastolic blood pressure decreased by 16.05 mmHg(P=0.003). The blood cortisol concentration at 8 am decreased by 8.23 μg/dL(P＜0.000 1), the 24-hour urinary free cortisol decreased by 273.21 μg/24 h(P＜0.000 1), and the average ACTH concentration increased by 6.40 pg/mL(P=0.006 2). CT examination showed that there was no significant change in the contralateral adrenal gland of the patients without recurrence during the follow-up period. There was no recurrence in 6 patients with subclinical AIMAH, and the blood pressure decreased or returned to normal. Thirteen patients had a certain time of remission after surgery, but recurred after 5-63 months, with an average of 27.38 months and a median relapse time of 18 months. Recurrent patients underwent total or partial resection of the contralateral adrenal gland. A total of 59 operations were performed in 46 patients.Conclusion: Patients with AIMAH should be classified. Unilateral adrenalectomy should be recommended as the first choice for the treatment of patients with AIMAH, which can avoid various complications caused by insufficient secretion of corticosteroids after bilateral adrenalectomy simultaneously, and can benefit the patients of all three subtypes after surgery. Patients should be followed up regularly after surgery. The abnormal enlargement of contralateral adrenal gland should be alert to the possibility of recurrence. Once it recurs, the contralateral adrenal gland needs to be treated. In the long run, unilateral adrenalectomy may benefit the patient for life, and there is a certain chance that the patient does not need to deal with the contralateral adrenal gland.