To study the effectiveness of AlloDerm (LifeCell Corporation, Branchburg, NJ) as a graft material in underlay tympanoplasty by comparison to autologous fascia in a chronic tympanic membrane perforation animal model.Seventeen chinchillas underwent creation of bilateral chronic tympanic membrane perforations over a 6-week period. Twenty-two stable perforations were divided equally between the experimental AlloDerm and control fascia graft groups. The grafts were surgically placed through a postauricular tympanomeatal flap. The tympanic membranes were examined at 4 and 10 weeks and then harvested for histopathological analysis. Tympanoplasty operative times, perforation closure rates, and gross and histological analyses were compared between the AlloDerm and fascia grafts.A statistically significant difference in mean surgical time was recorded between the AlloDerm (47 minutes) and fascia (68 minutes) grafting procedures (t test, P =.001). Perforation closure was achieved in 90% of the AlloDerm and 100% of the fascia treated tympanic membranes. Gross and histopathologic inspections revealed no significant differences. Microscopically, AlloDerm and fascia grafts had similar inflammatory responses, but AlloDerm showed increased fibroblast infiltration and neovascularization.The avoidance of donor site morbidity, reduction of surgical time, and excellent gross and histologic outcomes in this animal model reveal that AlloDerm could be a safe, cost-effective alternative to autologous fascia. Further study would be necessary in human clinical trials.