BACKGROUND We performed bilateral laparoscopic adrenalectomies on four patients (three women and one man) with Cushing's disease (pituitary-dependent Cushing's syndrome) showing persistent hypercortisolism after transsphenoidal surgery. METHODS The technique for bilateral transperitoneal laparoscopic adrenalectomy was derived from the one previously adopted by our group for unilateral adrenalectomy and previously described. Eight trocars were used, of which two were used for both left and right adrenalectomy. RESULTS Bilateral laparoscopic adrenalectomy was performed in a one-stage procedure in the three women and, because of the abundant abdominal fat of the patient, in a two-stage procedure (after a 1-week interval) in the man. Operating times for the three women were 255 minutes, 230 minutes, and 220 minutes, and for the man 170 minutes for right adrenalectomy and 140 minutes for left adrenalectomy. No surgical or anesthesiologic complications were encountered. All patients were discharged from the hospital within 5 days after operation. At present, after follow-up periods of 23, 8, 6, and 18 months, all patients show remission of Cushing's disease and undetectable cortisol levels. CONCLUSIONS Our experience suggests that bilateral laparoscopic adrenalectomy is a safe and effective procedure and a valid therapeutic option in patients with Cushing's disease showing persistent hypercortisolism after transsphenoidal surgery. However, the decision to remove both adrenal glands in such patients needs to be weighed against the risk of their having Nelson's syndrome or other long-term complications.