Bioartificial liver assist devices (BALs) offer an opportunity for critical care physicians and transplant surgeons to stabilize patients prior to orthotopic liver transplantation. Such devices may also act as a bridge to transplant, providing liver support to patients awaiting transplant, or as support for patients post living-related donor transplant. Four BAL devices that rely on hepatocytes cultured in hollow fiber membrane cartridges (Circe Biomedical HepatAssist(r), Vitagen ELADTM, Gerlach BELS, and Excorp Medical BLSS) are currently in various stages of clinical evaluation. Comparison of the four devices shows that several unique approaches based upon the same overall system architecture are possible. Preliminary results of the Excorp Medical BLSS Phase I safety evaluation at the University of Pittsburgh, after treating four patients (F, 41, acetominophen-induced, two support periods; M, 50, Wilson’s disease, one support period; F, 53, acute alcoholic hepatitis, two support periods; F, 24, chemotherapy-induced, one support period, are presented. All patients presented with hypoglycemia and transient hypotension at the start of extracorporeal perfusion. Hypoglycemia was treated by IV dextrose and the transient hypotension responded positively to IV fluid bolus. Heparin anticoagulation was used only in the second patient. No serious or adverse events were noted in the four patients. Moderate Biochemical response to support was noted in all patients. More complete characterization of the safety of the BLSS requires completion of the Phase I safety evaluation.