Acellular dermal matrix is frequently used in implant-based breast reconstruction to cover the inferior aspect of the breast pocket. Its performance profile remains equivocal. The authors studied whether adding it in implant-based immediate breast reconstruction improved outcomes when compared with non-acellular dermal matrix reconstruction. Patients undergoing implant-based immediate breast reconstruction at a single academic medical center were evaluated. Aesthetic outcomes and postoperative complications were assessed and direct comparisons were made between acellular dermal matrix and non-acellular dermal matrix cohorts. A total of 203 patients underwent 337 immediate expander-based breast reconstructions [with acellular dermal matrix, n=208 (61.7 percent); without, n=129 (38.3 percent)]. Patient characteristics, including age at time of reconstruction (mean, 49±11 versus 47±10 years) and body mass index (mean, 23±5 versus 23±3 kg/m) were similar between groups (p>0.05). Complications occurred in one-third of patients (33.5 percent). In univariate analyses, acellular dermal matrix use had fewer overall complications (odds ratio, 0.61; 95 percent CI, 0.38 to 0.97). The incidences of seroma/hematoma (p=0.59), infection (p=0.31), and wound complications (p=0.26) did not differ. Aesthetic outcomes were higher in the acellular dermal matrix group. In multivariate logistic regression, acellular dermal matrix use was associated with less capsular contracture (odds ratio, 0.18; 95 percent CI, 0.08 to 0.43) and mechanical shift (odds ratio, 0.23; 95 percent CI, 0.06 to 0.78). Optimizing the inframammary fold with acellular dermal matrix creates a superior aesthetic result. Its use appears safe and is associated with less capsular contracture and mechanical shift and improvement in the inframammary fold appearance, without increasing postoperative complications. Therapeutic, III.