Recently, the retroperitoneal laparoscopic approach has been described as advantageous in avoiding the respiratory and hemodynamic effects of CO2 pneumoperitoneum and giving direct access without the need to move abdominal organs. Forty-two laparoscopic adrenalectomies (LpA) were performed in 36 patients with a variety of adrenal disorders, including 9 patients with nonfunctioning tumors, 11 patients with aldosterone adenoma, 10 patients with Cushing's adenoma, and 6 patients with Cushing's disease. Twenty-two adrenalectomies were performed using the transperitoneal approach (TLpA), and 20 via the retroperitoneoscopic approach (RLpA). Arterial blood samples, mean arterial pressure, heart rate, and clinical parameters were evaluated. At the end of the operation, the PaCO2, PetCO2, and base deficit all increased significantly in both retroperitoneal and transperitoneal CO2 insufflation compared with basal values. Arterial pH decreased significantly in both TLpA and RLpA groups. All clinical parameters evaluated (operation time, analgesic dosing requirements, hospital stay, and the days until return to normal activity) were similar in the TLpA and RLpA approaches. Two patients in the TLpA (10.5%) group and two patients in the RLpA (10%) group needed conversion to open surgery. This study shows the safety and efficacy of laparoscopic adrenalectomy via the transperitoneal or retroperitoneal route in patients with a variety of adrenal disorders. The retroperitoneoscopic approach could be the primary choice in patients with previous abdominal surgery.