SummaryLaparoscopic approaches to adrenalectomy have been limited by the retroperitoneal (RP) location of the adrenal glands and their relative inaccessibility transabdominally. We developed a technique for endoscopic adrenalectomy in a domestic swine model using insufflation of the RP space with CO2and retroperitoneoscopy. The technique for retroperitoneal endoscopic adrenalectomy was first developed in an acute study of three animals. A chronic survival study was then undertaken in six pigs. Unilateral right (n = 3) or left (n = 3) adrenalectomy was performed. Mean RP insufflation time was 14.5 min (range, 7–30 min), and mean dissection time after insufflation was 100 min (range, 80–120 min). Two additional animals died under anesthesia after RP insufflation and placement of the trocars for retroperitoneoscopy but before dissection of the adrenal gland. One death was unexplained at autopsy. The other death was associated with a right-sided pneumothorax attributable to penetration of the diaphragm by a trocar. The remaining six pigs recovered uneventfully from the procedure. Autopsies performed 37 to 51 days postoperatively showed minimal scarring of the adrenalectomy bed. The results suggest that posterior adrenalectomy using RP CO2insufflation and direct retroperitoneoscopy is potentially applicable to the treatment of small adrenal lesions in humans.