Background: Despite relatively sparse data regarding their outcomes in the setting of infection, biologic grafts have gained rapid acceptance by the surgical community for complex hernia repair. These materials are heterogeneous in their procurement and processing techniques, which may ultimately have an impact in their ability to withstand infection. The objective of this study is to evaluate the impact of varying levels of contamination on biologic graft performance in a chronic ventral hernia animal model. Methods: Four commonly applied biologic grafts were used in the repair of a chronic ventral hernia rat model (n = 218). Each material was repaired in the setting of 1 of 4 surgical wound classifications (clean, clean contaminated, contaminated, dirty infected) with Staphylococcus aureus as our inoculum agent. After a 30-day survival, repairs underwent quantitative cultures, histological, and biomechanical testing. Results: Marked differences were observed in biologic graft bacterial burden, biomechanical and histological responses at 30 days. Persistent bacterial burden varied among the biologic grafts and increased with increasing wound contamination (P <.05). Delays in wound healing were observed in the contaminated and dirty infected setting (P <.05). Increasing infection weakened the biomechanical strength of repairs (P <.05). Conclusion: The degree of bacterial contamination at the time of repair affected the rates of bacterial clearance, wound-healing ability, and subsequent repair strength. Material source and processing techniques might alter graft durability, biocompatibility, and ability to clear bacteria in a contaminated field. Clinical trials are warranted in contaminated settings.