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• Effects of size, renal function, age (postnatal age, gestational age and postmenstrual age) as predictors of vancomycin clearance in premature neonates are established, but the relative contribution of each component remains poorly quantified, largely because these variables are closely correlated.

• We have quantified the covariates contributing to vancomycin clearance population parameter variability in order to establish the major covariates required for dosing predictions. Size, standardized using allometric models, was the primary covariate used in our analysis.

• Size explained 49.8%, postmenstrual age 18.2% and renal function 14.1% of clearance variability.

• Descriptors of the relationship between age and clearance in premature neonates vary.

• The use of a variable slope sigmoidal model to describe the relationship between …