The primary objective of this study is to investigate the feasibility and utility of developing a defensible safety case for disposal of United States Department of Energy (U.S. DOE) high-level waste (HLW) and DOE spent nuclear fuel (SNF) in a conceptual deep geologic repository that is assumed to be located in a bedded salt formation of the Delaware Basin. A safety case is a formal compilation of evidence, analyses, and arguments that substantiate and demonstrate the safety of a proposed or conceptual repository. A safety case also provides the necessary structure for organizing and synthesizing existing knowledge in order to help DOE prioritize its future research and development (R&D) activities. We conclude that a defensible initial safety case for potential licensing could be readily compiled by capitalizing on the extensive technical basis that exists from prior work on the Waste Isolation Pilot Plant (WIPP), work on other repository development programs, and the work published through international efforts in salt repository programs such as in Germany.It should be emphasized that the DOE has not made any decisions regarding the disposition of DOE HLW and DOE SNF. This study provides additional information that could be used to inform DOE's decision making regarding management of this waste. Furthermore, the safety case discussed herein is not intended to either site a repository in the Delaware Basin or preclude siting in other media at other locations. Rather, this study simply presents an approach for accelerated development of a safety case for a potential DOE HLW and DOE SNF repository using the currently available technical basis for bedded salt. This approach includes a summary of the regulatory environment relevant to disposal of DOE HLW and DOE SNF in a deep geologic repository, the key elements of a safety case, the evolution of the safety case through the successive phases of repository development and licensing, and the existing technical basis that could be used to substantiate the safety of a geologic repository if it were to be sited in the Delaware Basin. We also discuss the potential role of an underground research laboratory (URL).