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Agent-based models (ABMs) describe and simulate complex systems comprising unique agents, or individuals, while accounting for geospatial and temporal variability among dynamic processes. ABMs are increasingly used to study healthcare-associated infections (ie, infections acquired during admission to a healthcare facility), including Clostridioides difficile infection, currently the most common healthcare-associated infection in the United States. The overall burden and transmission dynamics of healthcare-associated infections, including C difficile infection, may be influenced by community sources and movement of people among healthcare facilities and communities. These complex dynamics warrant geospatially explicit ABMs that extend beyond single healthcare facilities to include entire systems (eg, hospitals, nursing homes and extended care facilities, the community). The agents in ABMs can be built on a synthetic population, a model-generated representation of the actual population with associated spatial (eg, home residence), temporal (eg, change in location over time), and nonspatial (eg, sociodemographic features) attributes. We describe our methods to create a geospatially explicit ABM of a major regional healthcare network using a synthetic population as microdata input. We illustrate agent movement in the healthcare network and the community, informed by patient-level medical records, aggregate hospital discharge data, healthcare facility licensing data, and published literature. We apply the ABM output to visualize agent movement in the healthcare network and the community served by the network. We provide an application example of the ABM to C difficile infection using a natural history submodel. We discuss the ABM's potential to detect network areas where disease risk is high; simulate and evaluate interventions to protect public health; adapt to other geographic locations and healthcare-associated infections, including emerging pathogens; and meaningfully translate results to public health practitioners, healthcare providers, and policymakers. Agent-based models describe and simulate complex systems comprising unique agents, or individuals, while accounting for geospatial and temporal variability among dynamic processes. They are increasingly used to study healthcare-associated infections, including Clostridioides difficile infection. The authors describe their methods of creating a geospatially explicit model of a major regional healthcare network using a synthetic population as microdata input. [ABSTRACT FROM AUTHOR]