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A number of different agricultural crops such as Miscanthus and switchgrass are under evaluation as potential biomass feedstock alternatives. Since agricultural operations are weather dependent, unfavorable weather can significantly impact the feedstock production as well as subsequent storage and supply activities. In particular, the systemic impact of regional weather patterns must be considered while developing and evaluating the feedstock harvest systems. This was achieved using the BioFeed modeling framework in this work. We developed the BioFeed model to simulate and optimize production and provision activities, including infrastructure requirements and operations, in regional biomass feedstock production systems. Weather effects are now incorporated in BioFeed with the inclusion of the probability of working day (pwd) parameter in the model. The pwd defines the fraction of days in a specific period such as two weeks that are suitable for field operations, and its value depends on a number of weather related parameters such as rainfall, snow depth, soil temperature, and soil moisture content. Model simulations were conducted for Miscanthus for values of pwd between 20%-100% and intended biorefinery capacities between 1000-6000 Mg d-1; and the impact on total cost and farm machinery requirements was quantified. Results indicated that if the harvest and handling system was designed assuming 100% pwd, lower pwd values exponentially increased the cost and decreased the biorefinery capacity that could be supported by the collection region. For Illinois with the average winter pwd of about 35%, ignoring weather patterns therefore led to 38% increase in total cost and 45% decrease in the supportable biorefinery capacity. BioFeed was then used to optimize the harvest system for a particular value of pwd. Simulation studies showed that this maintained the intended biorefinery capacity and led to a linear increase in total cost with decreasing pwd. The resulting optimum system required significantly larger fleet of farm machinery. For Illinois, the total cost increased by about 3.5%, but the total capital investment in farm machinery increased by almost 34%. These results emphasized that the consideration of weather impacts on farm productivity is extremely important when considering system design and operations.