Although venovenous bypass (VVBP) has been suggested to protect the kidneys during liver transplantation and its systematic use has therefore been recommended, this beneficial effect of VVBP has not been clearly demonstrated. In a prospective, randomized, controlled trial, 77 patients receiving liver transplants for chronic liver disease were allocated to be supported with VVBP (group 1, 38 patients) or not (group 2, 39 patients). Both groups were similar in relation to preoperative clinical and laboratory data and operative transfusion requirements. Inulin clearance and urinary β2-microglobulin and N-acetyl-β-D-glucosaminidase (NAG) excretion (to determine glomerular filtration rate and tubular damage, respectively) were measured at different perioperative periods (anesthesia induction, hepatectomy, anhepatic phase, biliary anastomosis, and 24 hours after surgery). A significant decrease in inulin clearance and increase in tubular damage markers were observed in the anhepatic phase, which only partly improved in the subsequent phases. No significant differences were observed between groups 1 and 2 at any perioperative phase, except during the anhepatic phase, in which a more marked renal function impairment occurred in group 2 patients. However, renal function on the 7th postoperative day and the need for hemodialysis/ hemofiltration during the 1st week were similar in both groups. Among 40 variables analyzed, only low mean arterial pressure at anesthesia induction was identified as an independent predictor for early postoperative severe renal failure (inulin clearance < 10 mL/min/1.73 m2 at the 24th postoperative hour), with no significant relationship between this complication and the use of venovenous bypass. Renal function markedly deteriorates during liver transplantation, and renal impairment persists during the early postoperative period. Because VVBP support is not associated with any clear benefit in renal function, its systematic use does not seem to be justified.