A new type of in situ product removal (ISPR) technique of expanded bed adsorption (EBA) bioreactor was studied to simultaneously produce extracellular propionic acid and intracellular vitamin B12 by Propionibacterium freudenreichii CICC 10019. Resin screening experiments showed that the ZGA330 resin have the best biocompatibility and highest adsorption for propionic acid. Through the EBA bioreactor, propionic acid could be recovered efficiently by semi-continuous recirculation of the unfiltered broth, which eliminated the feedback inhibition of propionic acid. Fed-batch fermentation was carried out using the EBA system, resulting in a propionic acid concentration of 52.5 g L-1 and vitamin B12 concentration of 43.04 mg L-1 at 160h, which correspond to product yields of 0.66 g g(-1) and 0.54 mg g(-1), respectively. The present study suggests that the EBA bioreactor can be utilized for the simple and economical production of propionic acid and vitamin B12 in a single fermentation process. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserved.