BACKGROUND: Acellular dermal matrices (ADMs) have become an essential material for implant-based breast reconstruction. No previous studies have evaluated the effects of sterility of ADM under conditions of radiation. This study compared sterile (irradiated) and aseptic (non-irradiated) ADMs to determine which would better endure radiotherapy. METHODS: Eighteen male Balb/C mice were assigned to the control group with no irradiation (group 1) or one of two other groups with a radiation intensity of 10 Gy (group 2) or 20 Gy (group 3). Both sterile and aseptic ADMs were inserted into the back of each mouse. The residual volume of the ADM (measured using three-dimensional photography), cell incorporation, α-smooth muscle actin expression, and connective tissue growth factor expression were evaluated. The thickness and CD3 expression of the skin were measured 4 and 8 weeks after radiation. RESULTS: In groups 2 and 3, irradiated ADMs had a significantly larger residual volume than the non-irradiated ADMs after 8 weeks (P<0.05). No significant differences were found in cell incorporation and the amount of fibrosis between irradiated and non-irradiated ADMs. The skin was significantly thicker in the non-irradiated ADMs than in the irradiated ADMs in group 3 (P<0.05). CD3 staining showed significantly fewer inflammatory cells in the skin of irradiated ADMs than in non-irradiated ADMs in all three groups after 4 and 8 weeks (P<0.05). CONCLUSIONS: Under radiation exposure, irradiated ADMs were more durable, with less volume decrease and less deposition of collagen fibers and inflammatory reactions in the skin than in non-irradiated ADMs.