Sugarcane bagasse is an abundant and geographically widespread agro-industrial residue with high carbohydrate content, making it a strong candidate feedstock for the bio-based economy. This study examines the use of the low-cost protic ionic liquid triethylammonium hydrogen sulfate ([TEA][HSO4]) to fractionate a range of South African sugarcane bagasse preparations into a cellulose-rich pulp and lignin. The study seeks to optimize pretreatment conditions and examine the necessity of applying a depithing step on bagasse prior to pretreatment.Pretreatment of five bagasse preparations, namely whole, industrially depithed, laboratory depithed (short and long fiber) and pith bagasse with [TEA][HSO4]:[H2O] (4:1 w/w) solutions produced highly digestible cellulose-rich pulps, as assessed by residual lignin analysis and enzymatic hydrolysis. Pretreatment under the optimized condition of 120 °C for 4 h produced a pretreated cellulose pulp with up to 90% of the lignin removed and enabled the release of up to 69% glucose contained in the bagasse via enzymatic hydrolysis. Glucose yields from whole and depithed bagasse preparations were very similar. Significant differences in lignin recovery were obtained for laboratory depithed bagasse compared with whole and industrially depithed bagasse. The silica-rich ash components of bagasse were seen to partition mainly with the pulp, from where they could be easily recovered in the post-hydrolysis solids.The five bagasse preparations were compared but did not show substantial differences in composition or cellulose digestibility after pretreatment. Evidence was presented that a depithing step appears to be unnecessary prior to ionoSolv fractionation, potentially affording significant cost and energy savings. Instead, lignin re-deposition onto the pulp surface (and, in turn, particle size and shape) appeared to be major factors affecting the conditioning of bagasse with the applied IL. We show that pith bagasse, a common by-product of paper making, can be successfully conditioned for high glucose release while allowing recovery of lignin and silica-rich ash. The glucose yields obtained for bagasse using [TEA][HSO4]-water mixtures were ~ 75% as high as for conventional aprotic ionic liquids such as [Emim][OAc]; this result is highly promising for commercialization of ionoSolv processing given [TEA][HSO4] is 40 times less expensive, thermally stable and recyclable.