Objective To analyze the clinical effect of low-margin incision with trans-retromammary space approach on multiple fibroadenoma of breast.Methods A total of 82 patients with multiple fibroadenoma of breast treated from December 2015 to December 2017 in the General Surgery Department of Yangdong District People’s Hospital were selected.The subjects were assigned to two groups, with 41 cases in each group.The low-margin group adopted low-margin incision with trans-retromammary space approach; while the conventional group adopted radical resection.The clinical indicators, overall satisfaction, and postoperative complications were compared.Results The operation time and Vancouver Scar Scale (VSS) scores of the low-margin group were shorter and lower than those of the conventional group (P＜0.05); however, the intraoperative bleeding volume and hospitalization time were not significantly different between the two groups (P＞0.05).The incidence rates of complications of the low-margin group (21.95%) and the conventional group (19.51%) were not different (P＞0.05).The satisfaction rate of the low-margin group (90.24%) was significantly higher than that of the conventional group (68.29%) (P＜0.05).Conclusion Low-margin incision with trans-retromammary space approach has a remarkable effect on multiple fibroadenoma of breast, and improves the aesthetic measures of postoperative scar and breast.