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Background: Catheter-associated urinary tract infections (CAUTIs) are a major source of avoidable hospital-acquired infections. The scientific evidence supports utilization of nurse-driven protocols to reduce CAUTIs. Purpose: The purpose of this quality improvement project was to update and implement an evidence-based CAUTI prevention protocol for the nursing staff on a medical-surgical unit in an adult acute care hospital to decrease the utilization of indwelling urinary catheters and CAUTIs. Theoretical Framework: Donabedian’s structures, processes, and outcomes (SPO) model was utilized as the framework for this project. Donabedian’s SPO model focuses on strong healthcare structures and processes to improve nurse, patient, and organizational outcomes. Methods: This project utilized a quantitative design. A convenience sample of 28 nurses from the medical-surgical unit of a South Florida hospital participated in the project. An educational intervention was delivered on CAUTI prevention based on guidelines from regulatory agencies, and the hospital existing protocol was updated and revised to reflect the guidelines. The sample was administered a short demographic survey, and 10-item pretests and posttests on CAUTI prevention before and after implementation of the standardized evidence-based protocol. To determine possible differences in nurses’ knowledge and perceptions of indwelling urinary catheters before and after the implementation, paired t tests were conducted. To determine if the proportions of days with urinary catheters were statistically significantly different 30 days before and after implementation of the standardized evidence-based guideline, a 2-proportion z-test was conducted. Results: On analysis of the pretests and posttests, a statistically significant difference was found in 6 of the 10 questions, indicating that nurses’ knowledge and perceptions of CAUTIs improved after the intervention (p < .001 to p < .043). After the intervention, urinary catheter days relative to patient days also decreased significantly (z = 5.562, p < 0.001). Conclusion: Implementation of an evidence-based nurse-driven protocol in a hospital in South Florida improved nurses’ knowledge and perceptions of CAUTI prevention. Nursing practice and healthcare delivery can benefit from development of such guidelines and educational interventions to empower nurses to better manage patients’ indwelling urinary catheters, and decrease the incidence of CAUTIs in hospitals.