OBJECTIVES The objective of this study was to characterize clinical outcomes when cefepime was used in a neonatal intensive care population. METHODS Data were extracted from the medical records of all full-term (40 weeks gestational age) patients up to 2 months of age and preterm patients up to 48 weeks postmenstrual age admitted to the neonatal intensive care unit (NICU) at a freestanding children's hospital between January 1, 2010, and December 31, 2013, who received at least 48 hours of cefepime. The primary outcome measure was a positive clinical response as defined by a normalization of white blood cell count and/or culture clearance. RESULTS Final analysis included 74 patients. Clinical response was evaluable in 43.2% (32 of 74) of courses. Of these, positive clinical response was observed in 81.3% (26 of 32). Overall patient mortality was 16.2% (12 of 74). Adverse effects (AEs) occurred in 14.9% (11 of 74) of courses. CONCLUSIONS Cefepime can be used safely with reasonable clinical response in a NICU population, but additional studies are needed to further determine cefepime-associated clinical outcomes.