A prospective observational study was performed to analyze the clinical course of critically ill children who require continuous renal replacement therapy (CRRT). Variables associated with prolonged CRRT were analyzed. Of the 174 children treated with CRRT, 32 (18.3%) required CRRT for >14 days and 20 (11.5%) for >21 days. Prolonged CRRT was more common in patients with heart disease and those requiring mechanical ventilation, hemodiafiltration, and higher doses of heparin. The same factors were found when patients with CRRT for >14 days and 21 days were studied. Overall mortality rate was 35.6%; it was slightly higher in patients on prolonged CRRT (43.7% with CRRT > 14 days and 45% with CRRT >21 days), though the differences were not statistically significant. We conclude that there were no differences in the pre-CRRT clinical characteristics, severity of illness, and renal function in critically ill children requiring prolonged CRRT. Prolonged CRRT was more frequently required by patients with heart disease and those on mechanical ventilation. Patients with prolonged CRRT required more frequent hemodiafiltration and higher doses of heparin. Mortality was slightly higher in children with longer CRRT, though this difference did not reach statistical significance.