AbstractLimitations of synthetic biomaterials for abdominal wall repair have led investigators to seek naturally derived matrices, such as human acellular dermis, because of their excellent biocompatibility and their ability to naturally interface with host tissues with minimal tissue response. In this study, we investigated two different biomaterials derived from human dermis (FlexHD acellular dermis and FlexHD acellular dermis‐thick) in a rabbit abdominal hernia repair model. One quarter of the abdominal wall was replaced with each biomaterial, and the animals were followed for up to 24 weeks. Rabbit hernias repaired with AlloDerm®, a commercially available acellular dermal matrix, and sham operated animals served as controls. Retrieved samples of these implants were assessed grossly and histologically. Collagen production measurements and tension studies were performed. FlexHD acellular dermis, FlexHD acellular dermis‐thick, and AlloDerm® maintained their strength in the rabbit hernia repair model with no incidence of hernia formation or bowel adhesion. The exact size measurements at 24 weeks were 217.0 ± 20.9% for FlexHD acellular dermis, 200.8 ± 23.5% for FlexHD acellular dermis‐thick, and 209.7 ± 32.9% for AlloDerm®. Macroscopic and microscopic evaluation showed excellent integration and tissue formation. All biomaterials studied harbored cells that produced new collagen fibers, and a six‐fold increase in these fibers was observed at 24 weeks. This study shows that acellular biomaterials derived from human dermis are suitable for abdominal hernia repair. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res 2010