Several technologies for microalgae oil extraction are being evaluated in order to find the most adequate for large scale microalgae processing. In this work, exergy analysis was used as an instrument for screening three design alternatives for microalgae oil extraction in a large-scale process and as a decision-making tool for evaluation and selection of novel technologies from the energy point of view. Routes were simulated using dedicated industrial process simulation software, taking as feedstock a representative and robust modeled composition of Chlorella sp. microalgae biomass. Mass, energy and exergy balances were performed for each alternative, and physical and chemical exergies of streams and all specific microalgae constituents modeled were calculated with the help of the thermodynamic properties of biomass components and operating conditions of streams. Exergetic efficiencies, total process irreversibilities, energy consumption and exergy destruction were calculated for all solvent-based microalgae oil extraction pathways evaluated. It was shown that exergy analysis led to identify the hexane-based oil extraction (HBE) as the most adequate alternative of the routes assessed for scaling up from the energy point of view, presenting a maximum exergy efficiency of 51% and exergetic losses of 982,000 MJ considering a production of 104,000 t of microalgae oil per year. (C) 2012 Elsevier Ltd. All rights reserved.