Objective To evaluate the application effect of acellular dermal matrix (ADM) in immediate breast reconstruction after mammary mastectomy with prosthetic implants. Methods The clinical data of 68 patients with breast cancer undergoing immediate breast reconstruction with prosthetic implantation in our hospital were retrospectively analyzed and divided into ADM group (n=43) and non-ADM group (n=25), according to the use of ADM in the posterior space of pectoralis major muscle while prosthesis implantation or not. The size of breast prosthesis, operative time, intraoperative blood loss, drainage duration, total drainage, total hospital stay, postoperative complications, postoperative cosmetic effect and quality of life of patients were compared between the two groups. Results Patients in the ADM group showed no statistically significant difference regarding operative time, drainage duration, total drainage, hospital stay, postoperative complications and intraoperative removed gland volume with the non-ADM group (P>0.05). The average intraoperative blood loss in the ADM group was less than that of the non-ADM group, the average volume of prosthesis in the ADM group was bigger than that of the non-ADM group, the volume difference between prosthesis and removed gland in the ADM group was smaller than that of the non-ADM group, which was considered statistically significant difference (P<0.05). The subjective satisfaction and objective measurement scores of patients in the ADM group were significantly better than those of the non-ADM group, especially in the symmetry of breast, surgical scar and distance of lateral displacement of nipple (P<0.05). The postoperative quality of life in the ADM group was significantly better than that of the non-ADM group in terms of body image, sexual function and sexual interest (P<0.01). Conclusions It is safe and feasible to use ADM-assisted the immediate breast reconstruction after nipple-sparing mammary mastectomy with prosthetic implantation. As an extension of the pectoralis major muscle, ADM can enlarge the posterior space for the prosthesis implantation, making the choice of the prosthesis much more easier. The combined application of ADM can obtain a better cosmetic effect, meanwhile improving the postoperative quality of life and satisfaction of patients.