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• Wheat-fava bean rotation showed a better productivity than wheat-wheat rotation regardless the soil water holding capacity. • Wheat-fava bean rotation has shown less economic risk than other wheat based rotations. • Wheat-potato is the most profitable rotation, yet the most economically risky one. • Inputs-use efficiency of wheat would significantly increase when cultivated in deep soils. The promotion of optimum rotations and agricultural management of winter wheat-based cropping systems is very critical, as wheat is considered an essential component in the Mediterranean diet. Considering the delicate economic situation of farmers in the Mediterranean area, recommending a low risk, sustainable farming system is desirable. In this study, an innovative application of a multi-criteria field-level approach is presented, targeting food security, farmer profitability and environmental sustainability. The CropSyst biophysical simulation model was calibrated and implemented for the study site. It was chosen for its agro-environmental robustness to simulate four rotations (wheat-wheat, wheat-fallow, wheat-potato, and wheat-fava bean). Four types of wheat agricultural management systems (full fertilization and full irrigation, full fertilization and zero irrigation, zero fertilization and full irrigation, and zero fertilization and irrigation) were tested in low and high soil water holding capacity (WHC) types. The effects of soil conditions, management practices and rotation type on wheat grain yields were assessed. Furthermore, the performance of each winter wheat-based cropping system was evaluated in terms of productivity (protein production and profitability) and the efficient use of resources (nitrogen and water), as well as the economic risk of low relative productivity each one engenders. The results show that there is no particular optimal scenario that can simultaneously ensure high productivity, reduce economic risk of low relative productivity, and achieve high wheat- water- and nitrogen-use efficiency. However, the wheat-fava bean rotation cultivated with no wheat fertilization appeared to be a better substitute to the wheat-wheat rotation in terms of protein production (0.93 t/ha versus 0.8 t/ha in low WHC soil and 1.34 t/ha versus 1.17 t/ha in high WHC). This cropping system achieved a higher net profit (2111 US$/ha versus 1222US$/ha in low WHC and 3550 US$/ha versus 2450 US$/ha in high WHC), showing high resource-use efficiency and was less risky for farmers. Moreover, a very high profit could only be attained with the wheat-potato rotation (8640 US$/ha and 12,170 US$/ha in low and high WHC, respectively), yet with low input-efficiency and high economic risk of low relative productivity. [ABSTRACT FROM AUTHOR]