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PURPOSE This study aims to determine the optimal vancomycin dosing in critically ill patients with acute kidney injury receiving continuous renal replacement therapy (CRRT) using Monte Carlo simulation. METHODS A one compartment pharmacokinetic model was conducted to define vancomycin deposition for the initial 48hours of therapy. Pharmacokinetic parameters were gathered from previously published studies. The AUC24/MIC ratio of at least 400 and an average of AUC0-24 at > 700mgh/L were utilized to evaluate efficacy and nephrotoxicity, respectively. The doses achieved at least 90% of the probability of target attainment (PTA) with the lowest risk of nephrotoxicity defined as the optimal dose. RESULTS The regimens of 1.75grams every 24hours and 1.5grams loading followed by 500mg every 8hours were recommended for empirical therapy of an MRSA infection with expected MIC ≤1mg/L, and definite therapy with actual MIC of 1mg/L. The probabilities of nephrotoxic results from these regimens were 35%. CONCLUSIONS A higher dose of vancomycin than the current literature-based recommendation was needed in CRRT patients.