This article compares the processes for wheat straw lignocellulose fractionation by percolation, counter-current progressing batch percolation and batch reaction at low NaOH-loadings (3–6% of DM). The flow-through processes were found to improve delignification and subsequent enzymatic saccharification, reduce NaOH-consumption and allow reduction of thermal severity, whereas hemicellulose dissolution was unaffected. However, contrary to previous expectations, a counter-current process did not provide additional benefits to regular percolation. The compressibility and flow properties of a straw bed were determined and used for simulation of the packing density profile and dynamic pressure in an industrial scale column. After dissolution of 30% of the straw DM by delignification, a pressure drop above 100 kPa m−1 led to clogging of the flow due to compaction of straw. Accordingly, the maximum applicable feed pressure and volumetric straw throughput was determined as a function of column height, indicating that a 10 m column can be operated at a maximum feed pressure of 530 kPa, corresponding to an operation time of 50 min and a throughput of 163 kg m−3 h−1. Biotechnol. Bioeng. 2016;113: 2605–2613.