BACKGROUND: Acellular dermal matrix (ADM) is commonly used in implant-based breast reconstruction due to improved soft-tissue support and control of the implant pocket and decreased capsular contracture. However, concerns about complications have prompted the FDA to request more clinical data. This large-scale study aims to examine perioperative outcomes of ADM use in breast reconstruction. METHODS: This study utilized a national insurance-based database to identify patients who underwent mastectomy between 2011 and 2019, with and without ADM. The groups were matched for age, region, and comorbidities. Complications within 90 days were compared using univariate and multivariate analyses. RESULTS: A total of 49,366 patients were identified with 26,266 patients in the ADM group and 23,100 in the non-ADM group. Infection rates (4.7% ADM versus 4.4% no ADM) and seroma rates (3.9% ADM versus 4% no ADM) were similar. However, the ADM group had a 1% higher rate of implant removal (4.9% ADM versus 3.9% no ADM, < 0.001). In direct-to-implant procedures, ADM use was associated with higher explantation rates (8.2% versus 6.3%, = 0.002). Multivariate analysis identified tobacco use, hypertension, depression, obesity, ADM usage, and direct-to-implant surgery as risk factors for implant removal. CONCLUSIONS: This study found comparable infection and seroma rates in implant-based breast reconstruction with and without ADM. ADM use was associated with a 1% higher risk of implant removal, with risk factors including tobacco use, obesity, hypertension, depression, and direct-to-implant procedures. Multicenter studies and registry data on prepectoral breast reconstruction are warranted to help interpret these findings.