Background Acute liver failure after major surgical procedures is associated with a high risk of multiple organ failure, including acute renal failure. The optimal time to initiate renal replacement therapy for acute renal failure is controversial because of the poor overall clinical outcomes. Study Design From July 2002 to January 2005, all patients who had no history of liver disease, but developed acute liver failure and subsequent renal failure requiring renal replacement therapy after major surgery, at a surgical intensive care unit, were retrospectively analyzed. Patients were divided into early or late dialysis groups based on an arbitrary blood urea nitrogen cut-off level of 80 mg/dL before renal replacement therapy. Results Eighty consecutive patients (21 women), with a mean age of 57.8 ± 17.0 (SD) years, comprised the study group. The late dialysis group (n = 26) had a higher ICU mortality rate (p = 0.02) and a lower renal function recovery rate (p = 0.02) than the early dialysis group (n = 54). Fifty-three (66.3%) patients died during their ICU stay. Independent risk factors for ICU mortality were renal replacement therapy modality (intermittent hemodialysis versus continuous venous-venous hemofiltration; odds ratio OR = 4.32, 95% CI 1.26 to 14.79; p = 0.02), predialysis APACHE II score > 20 (OR = 6.52, 95% CI 1.61 to 26.36; p < 0.01), and late dialysis (OR = 4.01, 95% CI 1.05 to 15.27; p = 0.04). Conclusions The mortality rate in postoperative patients with acute liver failure–associated acute renal failure was very high. Earlier initiation of renal replacement therapy, based on the predialysis blood urea nitrogen level, with continuous venous-venous hemofiltration might provide a better ICU survival rate.