Importance: Hospitals pose a threat to autistic children’s mental health. Adapting hospitals to meet children’s needs can address this issue. Objective: To determine the impact of an interprofessional program (Adaptive Care) to support autistic children’s mental health on nursing staff’s knowledge, efficacy, and confidence. Design: Pretest–posttest, quasi-experimental design. Setting: Large pediatric hospital. Participants: Nursing staff were the first participants in the program implementation. Approximately 300 nursing staff received training through the program, and 107 completed program evaluation surveys. Of these, 18 nursing staff completed both the pretest and posttest surveys approximately 1 yr apart. Intervention: Occupational therapy practitioners and other professionals developed and implemented the program, which consists of staff training and resources to adapt hospital physical and social environments and to ultimately improve patients’ hospital experiences. Outcomes and Measures: Researcher-developed, pilot-tested, online survey to assess knowledge, perceived effectiveness, confidence, and strategies that staff used while caring for autistic children in the hospital. Results: Respondents had increased effectiveness and confidence working with autistic children in the hospital after program implementation. Respondents reported significantly more strategies to care for autistic children. Conclusions and Relevance: Interprofessional collaboration and programming can positively affect social environments in the hospital by enhancing nursing staff’s self-efficacy, confidence, and strategies to support mental health and to enhance health care for autistic children. What This Article Adds: The Adaptive Care program is an example of occupational therapy practitioners and other interprofessional team members adapting physical and social health care environments to support autistic children’s mental health. This program was effective at increasing nursing staff’s self-efficacy, confidence, and strategies while caring for autistic children in the hospital. Positionality Statement: This article uses the identity-first language autistic people. This nonableist language describes their strengths and abilities and is a conscious decision.