In neurosurgical cases, problems related to wound healing can vary from simple wound dehiscence to multilayer defects. This study demonstrates an effective method to prevent persistent cerebrospinal fluid (CSF) leakage using reinforcing acellular dermal matrix in neurosurgical patients with wound dehiscence. A 52-year-old woman was admitted for management of recurrent glioblastoma. After tumor removal surgery, the patient experienced sustained CSF leakage from the wound despite reparative attempts. The plastic surgery team performed wound repair procedure after remnant tumor removal by the neurosurgery team. Acellular dermal matrix was applied over the mesh plate to prevent CSF leakage and the postoperative status of the patient was evaluated. No sign of CSF leakage was found in the immediate postoperative period. After 3 years, there were no complications including CSF leakage, wound dehiscence, and infection. We hereby propose this method as a feasible therapeutic alternative for preventing CSF leakage in patients experiencing wound problem after neurosurgical procedures.