Objective To evaluate the safety of immediate breast reconstruction using deep inferior epigastric perforator (DIEP) flaps in the patients after neoadjuvant treatment. Methods From January 2019 to February 2021, the data of patients with breast cancer undergoing total mastectomy and immediate breast reconstruction using DIEP flap in Comprehensive Breast Health Center, Department of General Surgery, Ruijin Hospital were collected. Comparison of clinicopathological features was done between neoadjuvant treatment group and control group. Univariate analysis was used to compare the rate of surgical complications between two groups. Results A total of 110 patients were enrolled with 23 cases (20.9%) in neoadjuvant treatment group and 87 cases (79.1%) in control group. None of carcinoma in situ (0 vs. 19.5%, P=0.003) and higher pTNM stage (P<0.001) was present in neoadjuvant treatment group compared with those in control group. However, there were no significant differences in the number of flap perforator of DIEP (P=0.472), the proportion of bipedicled flaps (P=0.489), operative time (P=0.651) and hospital length of stay (P=0.275) between two groups. No significant difference was found in the incidence of postoperative complications between two groups. Breast seroma was the most common recipient complication (13.0%, 3 cases) without donor complication in neoadjuvant treatment group. The most common complication was fat necrosis (12.6%, 11 cases) in recipient site and abdominal seroma (3.4%, 3 cases) in donor site of control group. Reoperation was done in one case (4.3%) of neoadjuvant treatment group and 4 cases (4.6%) of control group. DIEP flap necrosis with total flap loss occurred in 2 cases (2.3%) in control group, but none in neoadjuvant treatment group. Conclusions The imme-diate breast reconstruction with epigastric free flap for breast cancer patients after neoadjuvant treatment would be a safe surgical scheme.