OBJECTIVES:: To perform a cost-effectiveness analysis comparing intermittent (IRRT) with continuous renal replacement (CRRT) as initial therapy for acute kidney injury (AKI) in the intensive care unit (ICU). METHODS::  We modeled life year gained, the quality-adjusted life years (QALYs) and healthcare costs for a cohort of 1000 both in IRRT and CRRT patients in ICU setting. We used a 5-year time horizon. A Markov model with two health states for AKI survivors was designed: dialysis dependence and dialysis independence. We applied Weibull regression from published estimates to fit survival curves for CRRT and IRRT patients and to fit the proportion of dialysis dependence among CRRT and IRRT survivors. We then applied a risk ratio obtained from a Renal Therapy Services (RTS) internal registries, meta-analysis and a large retrospective cohort study to the fitted CRRT estimates in order to determine the proportion of dialysis dependence for IRRT survivors. Local costs were estimated from internal RTS sources. We conducted one way deterministic sensitivity analyses based on a range of differences for daily implementation cost between CRRT and IRRT and a range of risk ratios for dialysis dependence for CRRT as compared with IRRT. RESULTS::  CRRT was associated with QALY gaining compared with IRRT (1.052 versus 1.037). Despite higher upfront costs for CRRT in the ICU (COP 1,390,000 for CRRT versus $521,280 for IRRT in average), the 5-year total cost including the cost of dialysis dependence was lower for CRRT ($15,700,000 for CRRT versus $16,200,000 for IRRT on average). The base case incremental cost-effectiveness analysis showed that CRRT dominated IRRT. This dominance was confirmed by extensive sensitivity analysis. CONCLUSIONS::  Initial CRRT is cost-effective compared with initial IRRT by reducing the rate of long-term dialysis dependence among critically ill AKI survivors.