Fungal pretreatment of lignocellulosic biomass for bioethanol production is an environmental-friendly alternative to steam explosion. However, this biological pretreatment has been tested on a small scale, where most of the typical problems of solid-state fermentations (SSF), such as limited aeration or temperature control, are not observed. The main objective of this study was to assess the feasibility of the fungal pretreatment of lignocellulosic biomass (wheat straw) at a demonstration scale using the white-rot fungus Irpex lacteus to improve straw digestibility. Different configurations were evaluated for the design of a 22 L SSF reactor, but a versatile vertical design that can operate as a packed-bed and as a tray reactor was selected. The wheat straw digestibility obtained in the SSF bioreactor after 21 days of pretreatment (60.6%) was similar to that achieved on a small scale (57.9%). In addition, the most common online monitoring variables (temperature and CO2 production) correlate with the fungal action on wheat straw. As well as the weight loss, obtaining comparable results at flask and reactor scale (30 and 34.5%, respectively). Graphical abstract: [Figure not available: see fulltext.]