Continuous renal replacement therapy (CRRT) has proved to be beneficial for the treatment of critically ill patients with acute renal failure (ARF). The aim of this study is to determine the outcome and identify the predictors of mortality of critically ill patients treated with CRRT for ARF in the intensive care unit (ICU). This prospective cohort study of critically ill patients with ARF requiring CRRT admitted to the ICU was carried out at a tertiary care hospital in Saudi Arabia from 2002 to 2008. A total of 644 of 7173 patients with ARF required CRRT were studied. About 9% of the ARF patients required CRRT and comprised mainly those with medical causes, carrying a mortality of 64%. Multivariate analysis found high serum creatinine as an independent factor for better outcome and requirement of mechanical ventilation (MV) as an independent factor for worse outcome. In our cohort study, ARF requiring CRRT in the ICU was associated with a high mortality.