OBJECTIVE To compare the operative outcomes of obese patients undergoing laparoendoscopic single-site (LESS) retroperitoneoscopic adrenalectomy or standard laparoscopic (LAP) retroperitoneoscopic adrenalectomy. METHODS Between September 2011 and April 2015, 51 obese patients underwent LESS retroperitoneoscopic adrenalectomy and their operative outcomes were compared with 65 obese patients who underwent standard retroperitoneoscopic adrenalectomy by the same surgeon. In the LESS group, a single-port access was positioned in the lumbar incision. The standard retroperitoneal adrenalectomy technique was performed with a combination of conventional and curved LAP instruments. The following parameters were adopted: patient demographics, surgical details, perioperative complications, postoperative outcome data, and short-term outcomes. RESULTS The LESS group was comparable with the LAP group in terms of total operative time (70.4 ± 21.3 vs 65.5 ± 24.8 minutes, p = 0.26), hospital length of stay (5.7 ± 1.2 vs 6.1 ± 1.5 days, p = 0.12), and incidence of complications (4/51 vs 5/65, p = 0.98) for patients with similar baseline demographics. The LESS group had significantly shorter surgical incisions (2.8 ± 0.3 vs 5.3 ± 0.6 cm, p < 0.0001), lower in-hospital analgesic requirement (7.6 ± 3.3 mg morphine equivalent vs 10.5 ± 6.2 mg, p = 0.003), and significantly superior scar satisfaction score (9.3 ± 0.7 vs 7.6 ± 1.4, p < 0.0001) than the LAP group. Although estimated blood loss was greater in the LESS group (28.1 ± 10.6 vs 16.9 ± 7.2 mL in the LAP group, p < 0.0001), <50 mL overall blood loss was not clinically significant. During a mean follow-up of 20.2 months, no recurrences or deaths were documented in either group. CONCLUSIONS In properly selected patients, LESS retroperitoneoscopic adrenalectomy for obese individuals is technically feasible and safe in experienced hands, offering perioperative outcomes comparable with those of the conventional multiport approach, but with a superior cosmetic outcome.