•Continuous infusion vancomycin (CIV) provides more rapid target level attainment.•CIV provides protection from nephrotoxicity compared to intermittent infusion.•There are practical advantages in dose adjustment and monitoring with CIV. Vancomycin is a common and critical drug for empiric antimicrobial therapy in the infected burn patient. However, profound physiologic changes may impede the clinical effectiveness and amplify the potential nephrotoxicity of vancomycin. This was a retrospective cohort study at a large academic medical center and regional burn center. Patients with ≥10% total body surface area burn that received intravenous vancomycin were considered for study inclusion. Patients were assigned to the intermittent infusion or continuous infusion cohort if they received vancomycin for ≥48 h with ≥1 documented vancomycin serum concentration. The target steady state drug level for continuous infusion was 17−22 mg/L. The target steady state trough drug level for intermittent infusion was 15−20 mg/L. The primary efficacy and safety outcomes were time to therapeutic drug level and nephrotoxicity respectively. Thirty continuous infusion subjects with 88 plasma drug levels and thirty intermittent infusion subjects with 80 plasma drug levels were analyzed within the study period. There was a significant difference in the number of subjects that achieved a plasma vancomycin level within the target range during the course of therapy (73.3% for continuous infusion vs. 26.7% for intermittent infusion, p = 0.0003). The time to therapeutic level was 3.90 days for continuous infusion and 5.22 days for intermittent infusion (p = 0.0393). Nephrotoxicity occurred less frequently in the continuous infusion cohort (23.3% vs. 53.8%). Continuous infusion vancomycin was associated with more rapid attainment of target levels and a lower rate of nephrotoxicity.