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Acellular dermal matrix has been popularized as an adjunct to tissue expander or implant breast reconstruction given its utility in providing additional coverage and support for the inferior pole. This study was performed to assess the risk of postoperative complications associated with the use of acellular dermal matrix–assisted implant-based reconstruction.The authors performed a retrospective analysis of consecutive immediate breast reconstructions performed over a 6-year period. A total of 415 implant-based reconstructions were divided into two groups: tissue expander or implant-based reconstruction with or without acellular dermal matrix. Demographic information, comorbidities, oncologic data, adjuvant therapy, and complications were collected for comparison.A total of 283 patients underwent 415 immediate breast reconstructions (151 unilateral and 132 bilateral); 269 reconstructions were performed using tissue expander or implants with acellular dermal matrix, and 146 reconstructions were performed without acellular dermal matrix. The seroma and infection rates were higher in the acellular dermal matrix group (14.1 versus 2.7 percent, p = 0.0003, for seroma; 8.9 versus 2.1 percent, p = 0.0328, for infection). Multiple logistic regression analysis showed that acellular dermal matrix and body mass index were statistically significant risk factors for developing seroma and infection. The use of acellular dermal matrix increased the odds of seroma by 4.24 times (p = 0.018) and infection by 5.37 times (p = 0.006).Acellular dermal matrix has enhanced implant-based reconstruction and remains useful in immediate prosthetic breast reconstruction. It is associated, however, with higher rates of postoperative seroma and infection. Careful patient selection, choice of tissue expander/implant volume, and postoperative management are warranted to optimize overall reconstructive outcome.