Problem and Purpose: Invasive candidiasis (IC) has up to a 30% mortality rate in extremely low birth weight (ELBW) infants. Despite evidence supporting fluconazole prophylaxis, adherence to guidelines was inconsistent in a Level IV NICU. A chart audit revealed variability in inclusion criteria and adverse event monitoring related to fluconazole administration. This QI project aimed to standardize fluconazole prophylaxis among ELBW infants in the NICU by implementing and measuring adherence to an updated, evidence-based guideline. Methods: Implemented from August to December 2024, the revised evidence-based guideline clarified inclusion criteria, dosing, duration, and adverse effect monitoring. Weekly audits to track adherence and provider education were conducted, followed by post-education surveys. Implementation of central line (CL) discussions during daily interdisciplinary rounds were conducted to monitor CL use. The project included 27 infants, NICU providers, and pharmacists. Results: Overall, weekly guideline adherence improved from 76% to 83%. Fluconazole was initiated within 72 hours for 81.5% (n=22) of infants, with all 27 infants receiving the correct dosing and frequency. Clinical and laboratory findings were unremarkable for 77.8% (n=21) of infants. Mild AST elevation occurred in 18.5% (n=5), and 3.1% had oliguria (n=1). No IC cases were reported. The average CL dwell days decreased from 28 to 18. Conclusions and Implications: The use of an evidence-based fluconazole prophylaxis protocol may improve guideline adherence. Continued provider engagement, EMR integration, and expansion to satellite NICU sites will be key to sustaining progress and standardizing care.