Two predictive methods for determining serum vancomycin concentrations (SVCs) at a Veterans Affairs medical center were compared. The data for inpatients at the San Francisco Veterans Affairs Medical Center who received i.v. vancomycin and had vancomycin concentrations recorded in 2003 were included in this retrospective study. Creatinine clearance was estimated by the Cockcroft and Gault equation. Volume of distribution and creatinine clearance were calculated for each patient, using the Leonard and Boro method and the Rushing and Ambrose method. The Sheiner and Beal method for determining precision and bias was used to evaluate whether the two methods significantly differed in their ability to predict SVCs. Of the 223 patients identified, 122 patients were included, and 212 SVCs were analyzed. The population was mostly male and had a mean age of 64.1 years. There were no significant differences in 95% confidence intervals for relative precision and relative bias between the two methods. In patients whose weight was within 120% of their ideal body weight (IBW), the Leonard and Boro method was significantly more precise and less biased in predicting SVCs. In patients whose weight exceeded 120% of their IBW, the Rushing and Ambrose method was less biased and tended to be more precise, although the difference in precision was not significant. Both methods yielded similar predictability for SVCs in a veterans population. The Leonard and Boro method better predicted SVCs in patients weighing within 120% of their IBW, while the Rushing and Ambrose method appeared to be more appropriate for calculating vancomycin dosages in patients whose weight exceeded 120% of their IBW.