OBJECTIVES: The purpose of this study was to minimize unnecessary laboratory services for hospitalized neonates with hyperbilirubinemia by revising a local clinical practice pathway (CPP). METHODS: A retrospective cohort study was performed to compare the number of laboratory tests and blood draws in patients hospitalized with neonatal hyperbilirubinemia before and after implementation of a revised CPP. The study included infants with neonatal hyperbilirubinemia <14 days old admitted after their birth hospitalization between April 2017 and October 2019. Primary outcome measures included the total number of blood draws and the number of laboratory tests obtained per patient and length of stay. Secondary outcome measures included 7-day readmission rate, charges, and discharge bilirubin level. RESULTS: The median number of blood draws per patient after implementation of the CPP decreased to 2 (interquartile range [IQR], 2–3) compared with 3 (IQR, 2–3) before implementation (Poisson model–based estimated mean difference, 1.1; 95% confidence interval, 1.0–1.3; P = .018). The median number of laboratory tests per patient after implementation decreased from 4 (IQR, 3–6) to 3 (IQR, 2–4; Poisson model–based estimated mean difference, 1.3; 95% confidence interval, 1.2–1.5; P < .0001). There was no significant change in length of stay, readmission rate, charges, or discharge bilirubin level. CONCLUSIONS: Implementation of a revised CPP was associated with a significant decrease in the number of blood draws and laboratory tests per patient for infants admitted to the hospital for neonatal hyperbilirubinemia.