AbstractVancomycin dosing guidelines recommend using first‐order analytic calculations or Bayesian software along with two drug concentrations at steady state to confirm an area under the serum concentration versus time curve (AUC24), which is safe and efficacious for the treatment of serious methicillin‐resistant Staphylococcus aureus (MRSA) infections. Evidence supporting optimal vancomycin dosing for empiric or nonserious MRSA infections is sparse. A systemwide vancomycin dosing protocol applying the latest guidelines and a novel dosing strategy to estimate AUC was created by a large, multicenter healthcare organization. A dosing calculator was embedded in the electronic medical record, and an analytics tool was created to monitor the incidence and predictors of vancomycin‐associated acute kidney injury (VA‐AKI). The incidence of VA‐AKI was tracked over time and between hospitals to identify opportunities to reduce variation. This article describes the implementation of the vancomycin protocol and the use of informatics to ensure patient safety.