We evaluated vancomycin levels as recent guidelines for therapeutic monitoring of vancomycin (not available at the time these data were collected) recommend trough levels of 15 to 20 μg/mL; however, this may be more difficult to achieve in patients with accelerated vancomycin clearance, such as burn patients or recipients of continuous venovenous hemofiltration (CVVH) therapy. We retrospectively studied 2110 serum vancomycin levels of 171 patients admitted to the burn intensive care unit for more than 4 years and who received vancomycin by continuous infusion (CI) or intermittent infusion (II), with or without simultaneous CVVH. In-hospital mortality, 14- and 28-day mortality following vancomycin therapy were not different between dosing methods, although increased mortality was observed in the subgroup of patients receiving CI vancomycin empirically for clinical sepsis with negative blood cultures. More vancomycin was delivered to patients daily by CI than II, and therapeutic drug monitoring costs were similar. After controlling for differences in vancomycin dose by case matching with propensity scores, mean vancomycin levels were 20.0 ± 3.8 μg/mL for CI, vs 14.8 ± 4.4 μg/mL for II (P < .001). CI dosing resulted in similar levels with or without CVVH, whereas in II dosing, CVVH appeared to significantly decrease vancomycin levels. Although CI dosing was associated with higher vancomycin levels in general and fewer levels of <10 μg/mL, significant nephrotoxicity or neutropenia was not observed. Fifty-seven patients (33.3%) developed bacteremia, and 106 Gram-positive bacteria were recovered, including 63 Staphylococcus aureus. Recurrent bacteremia while receiving vancomycin was infrequent. The 90th percentile minimum inhibitory concentration (MIC₉₀) for vancomycin of 36 available S. aureus isolates tested by broth microdilution was 1.5 μg/mL. CI produced more frequent therapeutic vancomycin levels and less frequent subtherapeutic levels compared to II. However, therapeutic vancomycin levels were achieved infrequently by either method of dosing. Given equivalent therapeutic drug monitoring costs and the lack of a clear clinical benefit, the role of CI dosing remains to be defined in spite of practical and theoretical advantages, particularly when administered in the setting of CVVH.