BACKGROUND: Necrotizing enterocolitis (NEC) is the leading cause of mortality among preterm neonates with inflammatory bowel disease. While the prior use of antimicrobials is recognized as a risk factor for NEC, there is limited understanding of which specific antimicrobials pose a higher risk. This study aims to identify antimicrobials associated with an increased risk of NEC in neonates undergoing intensive therapy. METHODS: A retrospective cohort study assessed 594 neonates (mean gestational age: 33.2 ± 4.4 weeks; mean birth weight: 1978.3 ± 1010.2 g) receiving intensive care and antimicrobial treatment at a Brazilian Teaching Maternity Hospital. Multivariate logistic regression identified factors associated with NEC, serving as adjustment variables in examining the relationship between prior antimicrobial use and NEC occurrence (p < 0.05). RESULTS: Risk factors for NEC included gestational age (OR 1.250, 95% CI 1.134 - 1.377), birth weight (OR 0.998, 95% CI 0.997 - 0.999), congenital heart disease (OR 4.777, 95% CI 2.217 - 10.293), methicillinresistant Staphylococcus aureus (MRSA) marker (OR 2.748, 95% CI 2.067 - 7.705), and prolonged hospitalization (OR 1.004, 95% CI 1.000 - 1.008). Meropenem, administered around the 17th day of hospitalization, preceded NEC diagnosis around the 34th day (17.5, 95% CI 10.6 – 24.4 vs. 34.5, 95% CI 20.3 – 42.7 days; p = 0.03). CONCLUSION: The prior administration of meropenem was associated with a higher incidence of NEC in neonates under intensive care.