To compare the surgical safety, cosmetic effect, and oncological safety between reverse endoscopic (R-E) and conventional open (C-O) bilateral mastectomy with total subpectoral implant-based reconstruction (IBR). Methods    Clinical data of 76 patients who underwent bilateral mastectomy with total subpectoral IBR at Breast Center, West China Hospital, Sichuan University from January 1, 2017, to April 30, 2019, were retrospectively analyzed. According to the operation method, they were divided into the R-E group (39 patients) and the C-O group (37 patients). The baseline data, intraoperative data, and postoperative complications were collected and compared between the two groups. Multivariate logistic regression analysis was used to analyze the influencing factors of surgical complications and postoperative patient satisfaction with the incision. Results    There was no significant difference in operation time between the two groups ［(314.7±91.8) min vs. (278.5±95.8) min, P=0.097］. Compared with the C-O group, the R-E group had a shorter follow-up time ［76(37,90) months vs. 38(27,51) months］ and a lower incidence of any surgical complications (63.9% vs. 10.3%). Besides, the scores of Scar-Q ［(34.0±8.4) vs. (81.2±10.9)］, Hurris and Ueda were higher , and the differences were statistically significant (P< 0.05). Multivariate logistic regression analysis showed that R-E surgery was an independent protective factor for postoperative surgical complications (OR=0.07, 95%CI 0.01-0.42, P=0.003) and an independent protective factor for postoperative patient dissatisfaction with the incision (OR=0.06, 95%CI 0.01-0.28，P=0.001). Local recurrence of the chest wall, axilla and supraclavicular region occurred in 1 patient in the R-E group at 6 months after operation, and 1 patient in the traditional open group had bone metastasis at 14 months after operation. There was no significant difference in the 24-month disease-free survival rate between the two groups (98.7% vs. 97.5%, P=0.648). Conclusion    The innovative R-E bilateral mastectomy with total subpectoral IBR significantly reduced the incidence of complications compared with C-O surgery, and the cosmetic effect is improved dramatically, which has broad application prospects.