BACKGROUND: Despite the widespread practice of using biologic scaffolds for soft tissue reinforcement over prosthetic implants, the impact of acellular dermal matrix (ADM) on surgical wound fluid biomarkers over the initial postoperative period after prosthetic breast reconstruction remains poorly understood. METHODS: Patients undergoing prosthetic breast reconstruction surgery where ADM was likely to be used were consented to have fluid samples collected from surgical drains after surgery. Sample collections occurred at an "Early" time point at 24 to 48 hours after surgery and then a "Late" time point approximately 1 to 2 weeks after surgery. All procedures were performed by a single surgeon. Acellular dermal matrix was placed when prosthetic coverage with autologous tissue could not be achieved. Laboratory analyses were performed in blinded fashion without the knowledge of whether the samples came from the ADM "Present" or "Not Present" group. RESULTS: Twenty-one patients were in the ADM Present group and 18 patients were in the Not Present group. Both groups showed similar demographics based on age and body mass index. Analyses for cell concentration, protein concentration, extracellular matrix protein levels, cell proliferation activity, and matrix metalloproteinase activity showed no significant differences between wound fluid samples from the 2 groups. CONCLUSIONS: The presence of ADM does not appear to significantly impact wound biomarkers in prosthetic breast reconstruction. The current study provides useful data regarding the impact of ADM on surgical wound fluid during the initial postoperative period, laying important groundwork for more extensive future studies on the impact of biologic scaffolds on wound biology.