Among critically ill patients, acute kidney injury (AKI) requiring dialysis is associated with mortality rates generally in excess of 50%. Continuous renal replacement therapies (CRRT) often are recommended and widely used, although data to support its superiority over intermittent hemodialysis (IHD) are lacking. Data from the Program to Improve Care in Acute Renal Disease (PICARD), a multicenter observational study of AKI, were analyzed. Among 398 patients who required dialysis, the risk for death within 60 d was examined by assigned initial dialysis modality (CRRT [n = 206] versus IHD [n = 192]) using standard Kaplan-Meier product limit estimates, proportional hazards ("Cox") regression methods, and a propensity score approach to account for selection effects. Crude survival rates were lower for patients who were treated with CRRT than IHD (survival at 30 d 45 versus 58%; P = 0.006). Adjusted for age, hepatic failure, sepsis, thrombocytopenia, blood urea nitrogen, and serum creatinine and stratified by site, the relative risk for death associated with CRRT was 1.82 (95% confidence interval 1.26 to 2.62). Further adjustment for the propensity score did not materially alter the association (relative risk 1.92; 95% confidence interval 1.28 to 2.89). Among critically ill patients with AKI, CRRT was associated with increased mortality. Although the results could reflect residual confounding by severity of illness, these data provide no evidence for a survival benefit afforded by CRRT. Larger, prospective, randomized clinical trials to compare CRRT and IHD in severe AKI are needed.