The main objective of this study was to fractionate prairie cordgrass (PCG) obtaining the highest cellulose digestibility. Following clean fractionation (CF) processing, the PCG lignocellulosic biomass was fractionated into three main building blocks: cellulose, hemicellulose and lignin. Effects of processing factors such as time, temperature, catalyst concentration and organic solvent mixture composition were evaluated. Organic solvent-aqueous mixture contained methyl isobutyl ketone (MIBK), ethanol and water in different proportions. Sulfuric acid was used as a catalyst. In order to evaluate the degree of pre-treatment, enzymatic saccharification was employed on the cellulose fraction obtained from the CF process. Response surface methodology was used for process optimization and statistical analysis. Optimal conditions (39 min, 154 degrees C, 0.69% catalyst and 9% MIBK) resulted in 84% glucose yield and 87% acid insoluble lignin (AIL). (C) 2011 Elsevier Ltd. All rights reserved.