When traditional process-design methodologies are applied to the conceptual design of biorefineries, the main drivers for their development are poorly considered. Biorefinery plants are facilities integrating biomass-conversion processes and equipment to produce fuels, energy, chemical intermediates, and end-use products. Appropriate design tools must consider their sustainability in terms of: (a) potential displacement of fossil fuels and materials, (b) mitigation of environmental impacts, (c) renewability, (d) economic feasibility, (e) biodiversity preservation, and (f) social responsibility. Performance on addressing these drivers should be assessed from appropriate environmental, social and economic perspectives. This paper illustrates the application of a methodology that incorporates these principles in the conceptual design of a switchgrass-based biorefinery. The results show that the proposed design complies with the definition of sustainability in 10 out of 11 indicators. The indicator Baseline-emissions reduction fell in the unsustainable range mainly due to the high SO2-eq and PO4-eq emissions over the life cycle of the proposed system, derived from fertilizers and pesticides application. The techno-economic analysis showed economic feasibility of the biorefinery when the minimum acceptable rate of return is below 12%. The proposed methodology shows great potential as a valuable complement to classic process design methodologies, by quantifying their sustainability during the conceptual-design stage, and requiring little extra effort beyond performing the techno-economic analysis and a life cycle assessment. (C) 2015 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.