Clinically applied bioartificial liver (BAL) support systems are difficult to compare with regard to overall hepatocyte-specific function and clinical outcome. We compared two clinically applied BAL systems, the Modular Extracorporeal Liver Support (MELS) CellModule and the AMC-bioartificial liver (AMC-BAL) in an in vitro set-up. Both BAL systems were loaded with 10 billion freshly isolated porcine hepatocytes, cultured for 7 days and tested on days 1, 2, 4 and 7. Average decrease in hepatocyte-specific functions over 7 days was 9.7%. Three parameters differed between both bioreactors: lidocaine elimination at days 1 and 2 was significantly higher in the AMCBAL, ammonia elimination showed a significantly higher trend for the AMC-BAL over 7 days and LDH release was significantly lower at day 7 for the MELS CellModule. In conclusion, this first in vitro comparison of two clinically applied BAL systems shows comparable functional capacity over a period of 7 days.