Bilayer dermal matrix substitute has been reported as being an alternative for more complex, autologous reconstructive options. A cost comparison analysis in the treatment of seven patients with complex wounds was performed. Methods: Seven consecutive patients reconstructed using bilayer dermal matrix substitute from a Level I trauma facility were retrospectively reviewed. Wounds included two resulting from necrotizing soft tissue infections, one diabetic lower extremity ulcer, and four traumatic wounds (two upper extremity, two lower extremity). The costs of hospital bed, surgeon, anesthesia and facility fees, and dermal matrix substitute were totaled. Physicians determined the most appropriate autologous reconstructive options. The costs of the autologous reconstructions based on averages at the same institution were compared with the actual costs of reconstruction using dermal matrices. Results: Cost benefit was noted in the two upper extremity traumatic wounds (2%, 59%). Negative benefit was noted in lower extremity wounds, and wounds resulting from infectious etiologies (range -7% to -529%, avg. -166%). Conclusion: Bilayer dermal matrix substitute can be a useful adjunct in reconstruction of complex upper extremity wounds or in critically ill patients. In patients with wounds of infectious origins, or in lower extremity trauma, autologous reconstruction may be more cost effective.