AbstractObjectives/Hypothesis:To compare the efficacy of acellular dermal matrix (ADM) and split thickness skin grafts (STSG) in oral cavity reconstruction.Study Design:Prospective cohort study.Methods:Thirty‐four patients were included in this study (ADM, n = 22; STSG, n = 12). Evaluation for patient demographics, graft site, graft contracture, and functional status as defined by the EORTC QLQ‐C30 and the H&N35 questionnaires. A subgroup of patients underwent graft site biopsy for histological analysis. A cost estimate of both procedures was also performed.Results:Patient groups were similar in age, sex, race, smoking exposure, and site grafted. More patients were treated with radiation therapy (pre‐ or postoperative) in the ADM group (45%) compared to the STSG group (17%). Graft failure rate was higher in the ADM group (14% vs. 0%), and both groups had similar estimated graft contraction. The quality of life survey results favored the ADM group, but only the category of trouble with social eating was statistically significant (P= .03). Radiation therapy had a significantly negative impact for both ADM and STSG. Histology demonstrated increased inflammation, fibrosis, and elastic fibers in the STSG group. The cost of the STSG was 3.5 times higher than the ADM group.Conclusions:Acellular dermis grafting for reconstruction of the oral cavity offers several advantages over STSG, including the lack of donor site morbidity, lower cost, a natural appearing mucosal surface, and comparable if not superior functional status. Lower graft survival rates for ADM in the setting of prior radiation and with thicker graft material was encountered. Laryngoscope, 2009