The biological process of converting lignocellulosic biomass into ethanol has the potential to reduce dependence on petroleum-based liquid fuels. If the ethanol product is to be competitive with current gasoline prices, improvements in processing costs are required. Specifically, the pretreatment step is often explored for process improvements because it plays a key role in downstream yields and productivity. The recently developed Co-solvent Enhanced Lignocellulosic Fractionation (CELF) pretreatment technology shows great potential in enhancing the biomass conversion economics, producing highly digestible solids that achieved economical ethanol titers of >50 g L-1 with near-theoretical yields at low to moderate enzyme loadings of 5 to 15 mg-protein g-glucan-1 and high solids loadings of >15%. Optimized conditions for CELF pretreatment with corn stover comprise of a 1:1 v:v ratio of tetrahydrofuran (THF) and water with 0.5% sulfuric acid reacted for 25 minutes at 150°C with 200 RPM stirring in a Parr reactor. Characterization of recovered solids show that the high digestibility was likely due to greater enzyme accessibility from high glucan composition after extensive lignin removal and hemicellulose solubilization, allowing for nearly-theoretical sugar and ethanol yields to be achieved at lower enzyme loadings than previously possible with other pretreatments. Specifically, high solids simultaneous saccharification and fermentation (SSF) of CELF and dilute acid (DA) pretreated corn stover shows that CELF achieved greater ethanol titers and yields in less time at a similar glucan and enzyme loading of 10-11% and 15 mg-protein g-glucan -1, respectively, with 58.8 g L-1 ethanol and 89.2% yield in 5 days as opposed to 47.8 g L-1 and 73.0% yield in ~21 days. Furthermore, the SSF of CELF pretreated corn stover achieved ethanol titers comparable to glucose fermentations with 86 g L-1 ethanol at 23% solids loading and15 mg protein g-glucan-1 enzyme loading, indicating that the major limiting factor in the process is related to the fermentative capability of the yeast strain. Optimization of SSF operating parameters shows that the best process parameters that resulted in near theoretical ethanol yields with Saccharomyces cerevisiae D5A were 20% solids and 10 mg-protein g-glucan-1, achieving 79.6 g L-1 at 89.6% yield in 7 days.