Catheter–associated urinary tract infections (CAUTI) lead to preventable harm and cost among hospitalized patients. In this quality improvement program, principles of human factors engineering were applied to reduce CAUTI at an academic medical center. Investigators utilized systems approaches to examine the factors related to CAUTI at their institution, including how the physical layout influenced adherence to best practices. They made changes based on this assessment, such as enhancing access to catheter maintenance supplies across all hospital units. The intervention also used technology (automated electronic health record reminders) and training (asynchronous education on catheter insertion) to augment safe catheter use. This multipronged approach led to a steep reduction in CAUTI at the end of the 3-year project compared to the preintervention period. The authors suggest that their results support the use of human factors engineering to decrease health care–associated infections.