Nurses and other health care providers face daily challenges when delivering care in the acute care settings to adult patients on the autism spectrum (ASD). Secondary to a lack of disability-specific training, health care providers may struggle to establish and maintain a therapeutic rapport with patients diagnosed on the autism spectrum (Bury et al., 2020). The purpose of this paper is to describe the development and pilot testing of decision-making tools to guide healthcare providers as they interact with patients on the autism spectrum using a novel approach. This mixed methods project employed simulation technology and actors portraying patients. It was conducted in two phases. During Phase 1, the decision-making tools were created using video-taped encounters between nursing students (n = 11) and standardized patients (actors) who displayed a range of core characteristics and behavioral features associated with ASD. During Phase 2, we piloted the tools with a convenience sample of 17 nurses. A panel of experts using a modified Delphi technique, 17-item task completion, 22-item behavioral encounter checklists and debriefing sessions, analyzed the 17-recorded simulations. The decision-making tools show promise of being to guide nurses' efforts to establish and maintain a therapeutic rapport with hospitalized adult patients who are also on the autism spectrum.