BACKGROUND/AIMS: The effect of high-flux (HF) dialysis on mortality rates could vary with the duration of dialysis. We evaluated the effects of HF dialysis on mortality rates in incident and prevalent hemodialysis (HD) patients. METHODS: Incident and prevalent HD patients were selected from the Clinical Research Center registry for end-stage renal disease (ESRD), a Korean prospective observational cohort study. Incident HD patients were defined as newly diagnosed ESRD patients initiating HD. Prevalent HD patients were defined as patients who had been receiving HD for > 3 months. The primary outcome measure was all-cause mortality. RESULTS: This study included 1,165 incident and 1,641 prevalent HD patients. Following a median 24 months of follow-up, the mortality rates of the HF and low-flux (LF) groups did not significantly differ in the incident patients (hazard ratio [HR], 1.046; 95% confidence interval [CI], 0.592 to 1.847; p = 0.878). In the prevalent patients, HF dialysis was associated with decreased mortality compared with LF dialysis (HR, 0.606; 95% CI, 0.416 to 0.885; p = 0.009). CONCLUSIONS: HF dialysis was associated with a decreased mortality rate in prevalent HD patients, but not in incident HD patients.