BACKGROUND To identify the differences in the vancomycin pharmacokinetics between multiple trauma patients and medically ill patients in the intensive care unit (ICU) stratified by the use of continuous renal replacement therapy (CRRT), and the factors affecting vancomycin clearance (CL). METHODS All the included patients received at least three consecutive doses of vancomycin, then, therapeutic drug monitoring was conducted. Patients' serum vancomycin trough levels and other clinical variables were identified retrospectively. The vancomycin pharmacokinetics and associated factors were compared and analyzed between trauma ICU (TICU) and medical ICU (MICU) patients. RESULTS In the non-dialyzed group, the CL was higher among the TICU patients than the MICU patients. However, in the continuous renal replacement therapy group, there was no significant difference in the CL between the multiple trauma and medically ill patients. The only factor associated with CL in the non-dialyzed group was creatinine clearance; none of the factors was associated with CL in the CRRT group. CONCLUSIONS In the case of non-dialyzed patients in the TICU, vancomycin dosages must be adjusted, depending on the patient's actual body weight changes. In the case of patients undergoing CRRT in both ICUs, vancomycin can be infused with fixed doses regardless of the patients' characteristics.