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Abstract: Radiation therapy is considered today an integral part of the management of breast cancer. However, radiotherapy significantly increases the incidence of total complications in breast reconstruction. Several procedures have been adopted to reduce complication rates in irradiated fields, including the use of acellular dermal matrices (ADMs). We conducted a retrospective analysis of our single-center experience with ADM-assisted implant-based reconstruction or revision surgeries for capsular contracture treatment in irradiated breasts. We divided our population into 4 groups based on prior surgical history: group A (previous quadrantectomy), group B (previous mastectomy and expander reconstruction), group C (previous mastectomy and implant reconstruction), and group D (prior quadrantectomy followed by mastectomy and implant reconstruction). At the European Oncology Institute in Milan, Italy, between June 2017 and April 2019, we identified 84 patients for a total of 86 irradiated breasts reconstructed with implant and ADM. We observed a total of 12 reconstructive failure, with the highest rate of failure in group B (16.6%) and in group D (15.38%). Overall, we recorded 22 total complications (24.4%): 12 major complications and 10 minor complications. The most common complication was infection, with 9 cases (10.4%), 6 of which were classified as severe and required implant removal. In group B, we observed the highest complication rate, both major and minor, with 7 of 42 patients (16.6%) experiencing each. Before reconstruction with ADM, the Baker grade ranged from 3 to 4, with a mean of 3.25. At the 2-year follow-up, the Baker grade ranged from 1 to 4, with a mean of 1.9. Surgeons were highly satisfied with the aesthetic result in 72.1% of cases, moderately in 8.1% and unsatisfied in 5.81%, and in 13.9%, the outcome was not assessable because of reconstructive failure. The worst aesthetic result was in group B. We observed significant reduction in capsular contracture in revision surgeries despite a moderately high rate of complications in previous quadrantectomy and radiotherapy. In our experience, breast reconstruction with implant and ADM is not the primary surgical indication in case of prior irradiation, but it can be considered as a valid alternative with reasonable safety profile, to be used in selected cases., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)