The use of acellular dermal matrix (ADM) is well established in scalp burn reconstruction. However, its application in at-risk patients and hostile scalp wounds remains controversial and only described in the pediatric setting. This study aims to describe the pre-operative factors leading to the decision to use ADM in adult patients undergoing complex scalp reconstruction, and to describe the postoperative outcomes including wound breakdown and need for reoperation. This is a retrospective case series of patients undergoing scalp reconstruction with use of ADM. Data was collected from operations performed by a single surgeon over a period from January 2017 to October 2018. Nine patients underwent scalp reconstruction including placement of ADM during the study period. Seven patients were female, and median age was 64 years. Six patients had undergone prior craniotomies and three had undergone prior craniectomies for a variety of etiologies including neoplastic disease (n = 4), aneurysmal disease (n = 2), and trauma (n = 3). Wound breakdown or delayed wound healing necessitated reconstructive operations in all patients, 4 of whom had exposed/infected hardware that required removal. The median area of soft tissue defects was 30 cm. Two of the 4 patients with both benign and malignant tumors had been treated with radiation therapy, compromising the quality of the remaining adjacent scalp. Acellular dermal matrix was used in each setting to augment or buttress thin scalp. In 4 patients cranioplasty implants, hardware, or mesh were replaced concurrently. Two patients proceeded onto staged alloplastic cranioplasty without complication. Median follow up was 115 days. During follow up, only 1 patient suffered a major complication requiring reoperation to explant an osteomyelitic bone flap. Acellular dermal matrix can serve as an adjunct in hostile scalp reconstruction. Augmenting the areas of compromised scalp, especially over alloplastic cranioplasty material, can minimize the likelihood of future hardware exposure. Our study demonstrates its use in high-risk scalp wounds defined by frequent operation, chronic infection, and radiation.