OBJECTIVE To investigate whether a decrease in cardiac output of >or=50% after vena cava clamping is associated with an increase in perioperative morbidity or mortality in patients undergoing orthotopic liver transplantation without venovenous bypass. DESIGN Retrospective, clinical study. PARTICIPANTS Patients undergoing elective orthotopic liver transplantation without venovenous bypass (n = 172). INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS In 82 patients (group 1), the decrease in cardiac output after vena cava clamping was >or=50%; in 90 patients (group 2), the decrease was <50%. Hemodynamics during surgery and perioperative morbidity and mortality were compared between group 1 and group 2 patients. Mean arterial pressure during the anhepatic phase was not significantly different between groups, but cardiac output and mixed venous oxygen saturation were significantly lower in group 1 patients. Perioperative mortality, need for postoperative renal replacement therapy, postoperative serum creatinine levels, and graft function were not different between groups. CONCLUSION A >50% reduction in cardiac output after vena cava clamping is not associated with an increase in perioperative morbidity and mortality when compared with patients with a less pronounced reduction in cardiac output. These results question the common practice of basing the indication for venovenous bypass during the anhepatic phase on a reduction in cardiac output of >50% after a trial of vena cava clamping.