Objective:To compare the efficacy and safety of retroperitoneal laparoscopic adrenalectomy (RLA) and transperitoneal laparoscopic adrenalectomy (TLA) in the treatment of localized adrenocortical carcinoma (ACC).Methods:The data of 22 patients with stage Ⅰ/Ⅱ ACC underwent laparoscopic adrenalectomy in our institution from January 2009 to December 2018 were retrospectively analyzed. According to the different surgical approaches, these patients were divided into RLA and TLA groups. Eleven patients underwent RLA and 11 patients underwent TLA. There were no significant differences between the RLA group and the TLA group in terms of age at first diagnosis[44 (35, 54) vs. 46(41, 55) years, P= 0.793], sex (male/female: 3/8 vs. 4/7, P = 1.00), secreting tumor ratio (3/11 vs. 4/11, P = 1.00), tumor location (left/right: 6/6 vs. 7/4, P = 1.00), with hypertension or diabetes mellitus (4/11 vs. 3/11, P = 1.00). However, RLA has significantly smaller tumor size [3.0(2.5, 8.4) cm vs. 7.7(5.2, 8.4)cm, P= 0.001], and more stage Ⅰ patients [90.9%(10/11) vs. 18.2%(2/11), P=0.002], compared with those in TLA group. The perioperative indicators and oncology prognosis outcomes were collected and compared between the two groups. The Kaplan-Meier method was performed to calculate the overall survival (OS) and disease-free survival (DFS). Results:Compared with TLA, RLA had shorter operation time[90(70, 100) vs. 110 (90, 120) min, P = 0.005] and postoperative drainage tube removal time [2 (2, 3) vs. 3 (2, 6) day, P = 0.002), and the difference was statistically significant. In the TLA group, one patient was converted to open operation due to intraoperative tumor capsule rupture. For postoperative complications, one patient in the TLA group suffered with wound infection. There were no perioperative deaths in either group. All postoperative pathological examinations confirmed ACC, and there was no significant difference in Ki-67 index between the two groups [10%(3%, 35%) vs. 10%(9%, 25%), P = 0.484]. The median follow-up was similar in the two groups [48(26, 98) vs. 31(18, 49) months, P=0.237]. The local recurrence and metastasis rates were 36.4% for RLA group and 63.6% for TLA group ( P = 0.395). Survival analysis showed no statistically significant difference in DFS [5-year DFS rate: 33.6% vs. 73.2%, P = 0.118] between the two groups. The 5-year OS rates for RLA group versus TLA group were 58.3% vs. 45.5% ( P=0.485). Conclusions:For localized (stage Ⅰ/Ⅱ) ACC, both RLA and TLA seem safe and feasible, based on the similar long-term oncological prognosis. However, compared with TLA, RLA has the advantage of shorter operation time and postoperative drainage tube removal time. Due to the small number of cases included in this study, further multi-center, large-sample studies are required to demonstrate clear benefit of one surgical approach in the future.