Objectives: The objectives of this research were to describe the interactions (formal and informal) in which macrocognitive functions occur and their location on a pediatric intensive care unit (PICU); describe challenges and facilitators of macrocognition using three constructs of space syntax (openness, connectivity, and visibility); and analyze the health care built environment (HCBE) using those constructs to explicate influences on macrocognition. Background: In high reliability, complex industries, macrocognition is an approach to develop new knowledge among interprofessional team members. Although macrocognitive functions have been analyzed in multiple health care settings, the effect of the HCBE on those functions has not been directly studied. The theoretical framework, “Macrocognition in the Health Care Built Environment” (m-HCBE) addresses this relationship. Methods: A focused ethnographic study was conducted, including observation and focus groups. Architectural drawing files used to create distance matrices and isovist field view analyses were compared to panoramic photographs and ethnographic data. Results: Neighborhoods comprised of corner configurations with maximized visibility enhanced team interactions as well as observation of patients, offering the greatest opportunity for informal situated macrocognitive interactions (SMIs). Conclusions: Results from this study support the intricate link between macrocognitive interactions and space syntax constructs within the HCBE. These findings help to advance the m-HCBE theory for improving physical space by designing new spaces or refining existing spaces, or for adapting IPT practices to maximize formal and informal SMI opportunities; this lays the groundwork for future research to improve safety and quality for patient and family care.