Background: Vancomycin is a commonly used antibiotic for the treatment of methicillin-resistant Staphylococcus aureus (MRSA), which requires therapeutic drug monitoring (TDM). Guidelines recommend targeting an individualized area under the curve/minimum inhibitory concentration (AUC/MIC) ratio of 400 to 600 mg × h/L to maximize efficacy and minimize the risk of acute kidney injury (AKI). Before these guidelines, the accepted method of vancomycin TDM was using trough levels alone. To our knowledge, no studies of veterans have compared the difference in AKI incidence and time in the therapeutic range between monitoring strategies. Methods: This single-site, retrospective, quasi-experimental study was conducted at the Sioux Falls Veterans Affairs Health Care System. The primary endpoint was the difference in vancomycin-induced AKI incidence between the 2 groups.Results: This study included 97 patients with 43 in the AUC/ MIC group and 54 in the trough-guided group. The incidence of vancomycin-induced AKI was 2% in the AUC/MIC group and 4% in the trough group (P = .10). The incidence of overall AKI for AUC/MIC-guided and trough-guided TDM was 23% and 15% (P = .29), respectively. Conclusions: We did not find a significant difference in the incidence of vancomycin-induced or overall AKI between AUC/MIC-and trough-guided TDM. However, this study did indicate that AUC/MIC-guided TDM of vancomycin may be more effective than trough-guided TDM regarding a quicker time to and higher overall time in the therapeutic range. These findings support the recommendation to transition to the use of AUC/MIC-guided TDM of vancomycin in the veteran population.