Abstract Agave bagasse is the lignocellulosic residue accumulated during the production of alcoholic beverages in Mexico and is a potential feedstock for the production of biofuels. A factorial design was used to investigate the effect of temperature, residence time and concentrations of acid and ethanol on ethanosolv pretreatment and enzymatic hydrolysis of agave bagasse. This method and the use of a stirred in-house-made mini-reactor increased the digestibility of agave bagasse from 30% observed with the dilute-acid method to 98%; also allowed reducing the quantity of enzymes used to hydrolyze samples with solid loadings of 30% w/w and glucose concentrations up to 225 g/L were obtained in the enzymatic hydrolysates. Overall this process allows the recovery of 91% of the total fermentable sugars contained in the agave bagasse (0.51 g/g) and 69% of total lignin as co-product (0.11 g/g). The maximum ethanol yield under optimal conditions using an industrial yeast strain for the fermentation was 0.25 g/g of dry agave bagasse, which is 86% of the maximum theoretical (0.29 g/g). The effect of the glucose concentration and solid loading on the conversion of cellulose to glucose is discussed, in addition to prospective production of about 50 million liters of fuel ethanol using agave bagasse residues from the tequila industry as a potential solution to the disposal problems.