Objective: Providing adequate soft tissue cover while preventing wound breakdown and infection can present a challenge when repairing large meningomyeloceles. Adding an extra barrier to protect the underlying dural elements in the event of complications should lower the morbidity and mortality associated with large repairs, which are at risk of dehiscence and subsequent exposure of the neural elements. Methods: Acellular cadaveric dermal matrix (ACDM) (AlloDerm, Life Cell Corporation, Branchburg, New Jersey) in freeze-dried sheets (thin, 0.2 mm and 0.4 mm), fixed with chromic sutures and placed over the dural repair and underneath associated soft tissue coverage/skin, which in our cases included lumbar fascial flaps, latissimus dorsi flaps, and skin flaps. The neural tube defects were repaired by neurosurgery, and plastic surgery performed the surface closure. A layer of ACDM was placed over the dural repair, fixed in place with chromic suture, and then covered with skin and soft tissue flaps. Results: In the series of 12 patients, there were 2 cases of wound dehiscence, one of which required secondary repair and closure. There were no long-term sequelae in our series. Conclusion: ACDM can be used as an added layer of protection in neurosurgical repair of large meningomyeloceles that are at risk for dehiscence.