BACKGROUND: Human acellular dermal matrix has become an increasingly used adjunct to traditional submuscular tissue expander/implant breast reconstruction, but there is no strong consensus regarding complication outcomes. This study stratified outcomes based on a meta-analysis of complications. METHODS: A query of the MEDLINE database for articles on human acellular dermal matrix and submuscular tissue expander breast reconstruction yielded 901 citations. Two levels of screening identified 48 relevant studies. The DerSimonian and Laird random-effects model was used to perform the meta-analysis. Risk ratios and pooled complication rates were calculated for each outcome of interest. RESULTS: Nineteen studies reporting human acellular dermal matrix (n = 2037) and 35 reporting submuscular outcomes (n = 12,847) were used to estimate complication rates. Rates were generally higher in acellular dermis patients: total complications, 15.4 versus 14.0 percent; seroma, 4.8 versus 3.5 percent; infection, 5.3 versus 4.7 percent; and flap necrosis, 6.9 versus 4.9 percent. Six studies reporting both acellular dermis and submuscular outcomes were used to estimate relative risks. There was an increased risk of total complications (relative risk, 2.05; 95 percent CI, 1.55 to 2.70), seroma (relative risk, 2.73; 95 percent CI, 1.67 to 4.46), infection (relative risk, 2.47; 95 percent CI, 1.71 to 3.57), and reconstructive failure (relative risk, 2.80; 95 percent CI, 1.76 to 4.45) in acellular dermis patients. CONCLUSIONS: The meta-analysis suggests that the use of human acellular dermal matrix increases complication rates vis-à-vis submuscular expander/implant reconstruction. This must be weighed against its reported advantages in enhancing cosmesis and ameliorating contracture. CLINICAL QUESTION/LEVEL OF EVIDENCE: : Therapeutic, III.