OBJECTIVE Vancomycin is commonly used in the neonatal population to treat Gram-positive bacterial infections. Despite frequent use, consensus on the ideal dosing regimen in low birth weight (LBW) neonates is lacking. The objective of this research is to determine how frequently vancomycin troughs within goal range (10–20 mg/L) are achieved with empiric dosing in critically ill neonates and infants weighing less than 2500 g. METHODS This retrospective review evaluated LBW infants who were admitted to a level IV NICU from January 2015 to December 2016. Patients were included if they had a vancomycin trough sample collected at steady state (after at least 3 doses). Three trough cohorts (subtherapeutic: <10 mg/L, therapeutic: 10–20 mg/L, and supratherapeutic: >20 mg/L) were compared with 1-way ANOVA for continuous data and a chisquare analysis for categorical data. RESULTS A total of 74 patients were included, with a mean birth weight (BW) of 819.7 ± 355.4 g and a mean gestational age (GA) of 26.4 ± 3.7 weeks. Only 27 patients (36.5%) had therapeutic vancomycin trough concentrations. Subtherapeutic troughs were recorded in 40 patients (54.1%), while supratherapeutic troughs were recorded in 7 patients (9.5%). Although there was no difference between the initial dose, initial frequency was significantly different between cohorts (p = 0.04). CONCLUSION Empiric dosing regimens do not produce vancomycin troughs within the goal range in most LBW patients. ABBREVIATIONS AUC24, 24-hour area under the concentration-time curve; BW, birth weight; GA, gestational age; LBW, low birth weight; MIC, minimum inhibitory concentration; MRSA, methicillin-resistant Staphylococcus aureus; NICU, neonatal intensive care unit; TDM, therapeutic drug monitoring.