Tissue expander/implant breast reconstructions by 5 surgeons at a single institution from 2005 to 2008 were retrospectively identified and divided into 2 cohorts: use of acellular dermal matrix (ADM, n = 75) versus standard submuscular placement (n = 52). The ADM group had a statistically significant higher rate of infection (28.9% vs. 12.0%, P = 0.022), reoperation (25.0% vs. 8.0%, P = 0.011), expander explantation (19.2% vs. 5.3%, P = 0.020), and overall complications (46.2% vs. 22.7%, P = 0.007). When stratifying by breast size, a higher complication rate was not observed with the use of ADM in breasts less than 600 g, whereas ADM use in breasts larger than 600 g was associated with a statistically significant higher rate of infection when controlling for the occurrence of skin necrosis. The ADM cohort had a significantly higher mean initial tissue expander fill volume (256 mL vs. 74 mL, P < 0.001) and a significantly higher mean initial tissue expander fill ratio (49% vs. 17%, P < 0.001). Further work is needed to define the ideal patient population for ADM use in tissue expander/implant breast reconstruction.