This study compares the perioperative results, aesthetic outcome and oncologic safety of single-port insufflation endoscopic nipple-sparing subcutaneous mastectomy combined with immediate reconstruction using prosthesis implantation (SIE-NSM-IRPI) with those of conventional open-nipple and areola-sparing subcutaneous mastectomy combined with immediate reconstruction using prosthesis implantation (C-NSM-IRPI).In this retrospective cohort study, 64 early-stage breast cancer patients were divided into SIE-NSM-IRPI (n = 38) and C-NSM-IRPI (n = 26) groups. Perioperative results (operation time, intraoperative blood loss, incision length, drainage duration, and recent complications) were then compared between the two groups. Differences in satisfaction with the breasts, psychosocial well-being, physical well-being (chest) and sexual well-being were analyzed according to the BREAST-Q scale, and survival outcomes were also compared.The median follow-up time was 51.5 months. The incision length of SIE-NSM-IRPI was shorter than that of C-NSM-IRPI (P < 0.001). SIE-NSM-IRPI achieved the same detection rate and median number of sentinel lymph nodes as C-NSM-IRPI (3.00vs. 4.00, P = 0.780). The incidence of prosthesis removal due to infection or prosthesis exposure in the SIE-NSM-IRPI group was lower than that in the C-NSM-IRPI group (P = 0.015). Satisfaction with breasts (82.00vs.59.00, P < 0.001), psychosocial well-being (93.00vs.77.00, P = 0.001) and physical well-being (chest) (89.00vs.82.00, P < 0.001) scores were higher in the SIE-NSM-IRPI group. There were no significant differences between the two groups in disease-free survival (hazard ratio = 0.829, 95% confidence interval = 0.182-3.779) and overall survival (hazard ratio = 1.919, 95% confidence interval = 0.169-21.842).In this selected cohort of patients with early breast cancer, SIE-NSM-IRPI was comparable to C-NSM-IRPI, considering oncologic safety and detection of sentinel lymph nodes. It had a lower incidence of prosthesis removal, shorter incision length, and was associated with better patient satisfaction with the breasts. More random clinical trials of this novel approach in a larger cohort of Chinese patients with an extended follow-up period are needed in the future.© 2023. The Author(s).