Current US transportation sector mainly relies on liquid hydrocarbons derived from petroleum and about 60% of the petroleum consumed is from areas where supply may be disturbed by regional instability. This has led to serious concerns on energy security and global warming. To address these issues, numerous alternative energy carriers have been proposed. Among them, second generation biofuel is one of the most promising technologies. Gasification-based thermochemical conversion will bring flexibility to both feedstock and production sides of a plant, thus presents an attractive technical route to address both the energy security and global warming concerns. In this paper, thermochemical ethanol production using multiple-feedstock (corn stover, municipal solid waste, and wood chips) is simulated using Aspen Plus and compared with the single-feedstock scenario, in terms of economic performances, life cycle greenhouse gas (GHG) emissions and survivability under extreme weather conditions. For a hypothetical facility in southwest Indiana it is found that multiple-feedstock strategy improves the net present value by 18% compared to single-feedstock strategy. This margin is increased to 57% when effects of extreme weather conditions on feedstock supply are considered. Moreover, multiple-feedstock fuel plant has no potential risk of bankruptcy during the payback period, while single-feedstock fuel plant has a 75% chance of bankruptcy. Although the multiple-feedstock strategy has 26% more GHG emission per liter of ethanol produced than the single-feedstock strategy, the trend is reversed if feedstock supply disruption is taken into account. Thus the idea of multiple-feedstock strategy is proposed to the future thermo chemical biofuel plants. (C) 2010 Elsevier Ltd. All rights reserved.