In this study, a three-stage oxidoreduction potential (ORP) control strategy was developed to improve propionic acid (PA) production using engineered Propionibacterium jensenii ATCC 4868 (pZGX04-gldA) in a 3-L bioreactor. Specifically, ORP was controlled at -200 mV from 0 to 36 h, -300 mV from 36 to 156 h, and -400 mV after 156 h. The PA titer increased from 21.38 to 27.31 g/L. The effects of ORP regulation on key intracellular metabolites were studied, demonstrating that ORP can both regulate NADH/NAD(+) ratio and the activities of some enzymes involved in electron transport and redistribute metabolic flux. We integrated the ORP control strategy with a fed-batch culture method and increased PA production to 39.53 g/L. This new ORP control strategy may be useful in the optimization of other anaerobic processes. (C) 2014 Elsevier Ltd. All rights reserved.