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Background: Critically ill patients undergoing Continuous Renal Replacement Therapy (CRRT) are treated with higher doses of fluconazole based on the literature recommendations. However, clinical follow-up data demonstrating the effectiveness of this approach are lacking., Purpose: A retrospective cohort study was conducted to evaluate whether target attainment was achieved with higher doses of fluconazole. Additionally, the study focused on identifying factors that may contribute to variability in fluconazole exposure in these patients., Methods: Critically ill patients undergoing Continuous Veno-Venous Hemodialysis (CVVHD) who received either standard or higher doses of intravenous fluconazole were included. Evaluation of target attainment was conducted for each dose regimen., Results: Administering higher doses resulted in target attainment in 100 % of the patients, indicating that starting with at least 400 mg twice daily is an adequate dosing guideline. In this study, only the dose of fluconazole was found to significantly influence target attainment (p < 0.001), with no other predefined factors identified as having a significant impact., Conclusion: According to the results of the study, increasing the fluconazole dose to at least 400 mg twice daily is sufficient to reach the desired target in critically ill patients undergoing CVVHD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)