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Background: The aim of this study is to perform a cost‐utility analysis of separated continuous renal replacement therapy (CRRT) compared with intermittent hemodialysis (IHD) in critically ill patients with acute kidney injury (AKI). Methods: Cost and clinical data were gathered from adult patients with AKI who received separated CRRT or IHD at a tertiary hospital in Thailand. We applied a Markov model in this study. Our primary outcome was the incremental cost‐effectiveness ratio (ICER). We performed sensitivity analysis to assess the influence of parameter uncertainty. Results: We enrolled 199 critically ill patients with AKI. Of these patients, 129 underwent separated CRRT, and the rest underwent IHD. The mortality rate and dialysis dependence status were not significantly different between the groups. The total costs of separated CRRT were lower than IHD ($73 042.20 vs. $89 244.37). We estimated that separated CRRT increased quality‐adjusted life years (QALYs) by 0.21 compared with IHD. The ICER of −74 035.16 USD/QALY gained in the case‐based analysis indicated that separated CRRT is superior to IHD due to the lower cost and more cumulative QALYs. After performing sensitivity analysis by varying parameter ranges, separated CRRT remained a cost‐saving approach. Conclusions: Separated CRRT is a cost‐saving modality compared with IHD in critically ill patients with AKI. This approach can be applied in resource‐limited settings. [ABSTRACT FROM AUTHOR]