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Background: Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in preterm infants. Survivors may suffer both short- and long-term morbidities. Current evidence suggests that the incidence of NEC can be reduced by standardizing the care delivery in addressing key risk factors including an altered gut microbiome, use of formula milk, hyperosmolar feeds, and unrestricted use of high-risk medications METHODS: Since 2014, the department has a workgroup who analyzed all cases of NEC within a month of diagnosis to identify preventable risk factors. Existing evidence-based quality improvement strategies were revised and new ones were implemented sequentially over the next 4 years. These strategies include (1) a standardized feeding protocol, (2) early initiation of enteral feeding using human milk, (3) optimization of the osmolality of preterm milk feeds using standardized dilution guidelines for additives, and (4) promotion of healthy microbiome by use of probiotics, early oral care with colostrum and by restricting high-risk medications and prolonged use of empirical antibiotics RESULTS: Baseline characteristics of the patients including sex, gestational age, and birth weight were similar during the study period. After implementing the evidence-based practices successively over 4 years, the incidence of NEC in very- low birth-weight (VLBW) infants dropped from 7% in 2014 to 0% (P < .001) in 2018. The duration of parenteral nutrition, use of central line, and days to full feeds were also reduced significantly (P < .05) CONCLUSION: Adopting evidence-based best practices resulted in a significant decrease in the incidence of NEC and improved the nutrition outcomes in VLBW infants., (© 2020 American Society for Parenteral and Enteral Nutrition.)