Sequential 2k factorial and central composite designs were used to optimize Agave tequilana bagasse (ATB) pretreatment by using 1-ethyl-3-methylimidazolium acetate ([Emim][OAc]). Reaction time, temperature and solids loading were the studied factors while sugar yield was the response variable. Results indicated that optimal conditions (119 °C, 142 min) using high solids loading (30%) were achieved at lower temperatures and reaction times than those previously reported in the literature. It was also revealed that solid recovery after pretreatment with [Emim][OAc] is a key factor. The increase in enzymatic digestibility of pretreated ATB was correlated to a decrease in crystallinity and lower lignin content as observed using microscopy techniques and weaken chemical bonds by Fourier transform infrared spectroscopy. Yields of glucose and xylose in the hydrolysate were 41.3, and 13.0 kg per 100 kg of untreated ATB, which are equivalent to glucan and xylan conversions of 75.9% and 82.9%, respectively.