The purpose of this study was to fractionate switchgrass (SG) to obtain hemicellulose-, lignin-rich fractions and highly digestible pulp, using a clean fractionation (CF) approach. The main objective was to produce highest glucose yield in the enzymatic hydrolysis of pulp. Effects of processing factors such as time (10-50 min), temperature (120-160 degrees C), catalyst concentration (0.21-0.93% w/w sulfuric acid) and organic solvent mixture composition (7-43% w/w methyl isobutyl ketone) were evaluated. Response surface methodology and central composite design were used for process optimization and statistical analyses. High lignin (75-93%) and xylan (83-100%) removal from biomass were obtained, leaving solid pulp rich in glucan (78-94%). High enzymatic hydrolysis glucose yields (more than 90%) were obtained for selected optimal conditions. Pulp can be used for ethanol production while separated xylan and lignin fractions can be used as a feedstock for value-added products which suggests the applicability of clean fractionation technology in a biorefinery concept. (C) 2012 Elsevier Ltd. All rights reserved.