Background <p>Cushing’s syndrome is a systemic disorder caused by prolonged exposure to excessive glucocorticoids and is associated with significant morbidity and increased mortality. Minimally invasive adrenalectomy has become the preferred surgical approach for adrenal tumors due to favorable perioperative outcomes. This study aimed to evaluate the clinical characteristics, surgical outcomes, and histopathological findings of patients who underwent minimally invasive adrenalectomy for overt Cushing’s syndrome and mild autonomous cortisol secretion (MACS).</p> Methods <p>This retrospective study included 114 consecutive patients who underwent minimally invasive adrenalectomy between January 2006 and December 2025 at our institution. The diagnosis of cortisol excess was established through multidisciplinary evaluation. Hormonal assessment consisted of late-night salivary cortisol measurements, 24-hour urinary free cortisol levels, adrenocorticotrophic hormone (ACTH), and a 1-mg dexamethasone suppression test. Patients with typical clinical features of hypercortisolism and abnormal hormonal findings were classified as having overt Cushing’s syndrome, whereas patients without overt Cushingoid features but with a post-dexamethasone suppression test cortisol level &gt; 1.8&#xa0;µg/dL were classified as having MACS. Demographic characteristics, clinical manifestations, radiological findings, surgical approach, postoperative complications, histopathological and clinical outcomes were analyzed.</p> Results <p>The mean age of the patients was 47.8 ± 12.4 years, and the female-to-male ratio was 100:14. Adrenalectomy was performed on the right adrenal gland in 43 patients (37.7%), on the left adrenal gland in 62 patients (54.4%), and bilaterally in 9 patients (7.9%). Transabdominal laparoscopic adrenalectomy (TLA) was performed in 111 patients (97.4%), and posterior retroperitoneoscopic adrenalectomy (PRA) was performed in 3 patients (2.6%), with no conversion to open surgery. The mean hospital stay was 4 days. Postoperative complications were rare and mostly minor, with no mortality or major complications. Histopathology revealed adrenocortical adenoma in 76 cases (61.8%), hyperplasia in 39 (31.7%), carcinoma in 3 (2.4%), and other benign lesions in 5 (4.1%). Among patients with available postoperative hormonal follow-up, biochemical remission was achieved in 88.8% of patients, while profound cortisol suppression (&lt; 2&#xa0;µg/dL) was observed in 75.0% of patients. Adrenalectomy was also associated with significant postoperative improvements in metabolic parameters, particularly LDL cholesterol and triglyceride levels.</p> Conclusions <p>Minimally invasive adrenalectomy is a safe and effective treatment option for patients with overt Cushing’s syndrome and MACS. The low complication rate and absence of perioperative mortality observed in this study support the role of minimally invasive surgery in appropriately selected patients and highlight the importance of management in experienced, high-volume endocrine surgery centers.</p>