Clostridioides difficile infection (CDI) causes nearly half a million diarrheal illnesses annually in the United States and is associated with a twofold increase in the risk of death for hospitalized patients with CDI. Broad spectrum antibiotic therapy is a major risk factor for CDI. As such, healthcare-associated (HA) CDI is often employed as a metric to evaluate antimicrobial stewardship programs (ASPs). However, because the risk from antibiotics is heterogeneous and dependent on a variety of other individual and environmental risk factors, evidence that HA-CDI is a quality metric for stewardship success is lacking. The objective of this dissertation is to achieve a more granular understanding of the risk of HA-CDI from antibiotics, and to evaluate the specific contexts where we would expect HA-CDI incidence to reflect changes in broad spectrum prescribing through stewardship interventions.