Background: Procalcitonin (PCT) use is not widespread in the neonatal population during late-onset sepsis evaluations. Minimal data exist on appropriate PCT cutoff levels to treat with antibiotics for neonatal sepsis. New guidelines were implemented in select central Texas neonatal intensive care units for late-onset sepsis (infants older than 72 hours) with recommended PCT cutoff levels for antibiotic administration. Purpose: To evaluate antibiotic usage in a local neonatal population following late-onset sepsis workups pre-/postimplementation of a PCT guideline. Methods: A retrospective pre–/post–quality improvement project using chart review data was performed over 11 months in 2018. Inclusion criteria were infants older than 72 hours of life having a late-onset sepsis workup. The outcome measure is appropriate antibiotic administration, based on laboratory test results or cultures, for infants pre-/post-PCT guidelines. Results: The χ2 test indicated that the proportion of infants receiving appropriate antibiotics pre-/postinitiation of PCT guidelines did not significantly differ. There is, however, clinical significance with an improvement in the proportion of appropriate antibiotic administration and a decrease in variability. Implications for Practice: Using PCT may help the practitioner identify sepsis earlier and more effectively, thereby reducing morbidity and mortality among neonates while improving antibiotic stewardship. Implications for Research: The small sample size in this study and the limited number of neonatal intensive care units limit any inferences. Future research should evaluate the use of PCT in a larger sample across multiple settings.