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Abstract: We studied the effect of prospective climate change upon crop yield, and related water footprint of maize (Zea mays L.) for a relevant case study area in the Po valley of Northern Italy. To simulate maize production we used a cropping system simulation model CropSyst, which we set up and validated by way of crop yield data during 2001–2010. We then calculated the present water footprint (green, blue) of maize in the area, defined as the absolute and specific (per kg yield) amount of water evapotranspired during growing season, under three irrigation scenarios, namely (i) no irrigation, (ii) manual irrigation at fixed dates, and (iii) automatic irrigation on demand. We then evaluated the effects of prospective climate change upon maize production until mid-century (2045–2054), and we quantified the water footprint therein. We considered climate variations with focus upon temperature, precipitation, and CO2. First, we assessed maize yield and water footprint sensitivity to potential changes of these weather variables. We then fed the maize yield model with properly downscaled climate projections (storyline A2, business as usual) from global circulation models (GCM), included within the board of the Intergovernmental Panel of Climate Change, IPCC, and with those from a local scenario LOC, obtained by projecting recently observed local climate trends (1975–2010). Under the worst, more likely future scenarios of increasing temperature and decreasing precipitation, crop yield decreased and water footprint, especially blue, increased, due to increased evapotranspiration, higher irrigation demand, and lower final yield. Increase of CO2, albeit possibly increasing water use efficiency, seemed not to affect the water footprint noticeably. A possible increase of precipitation as projected by some GCMs, may partly make up for the increase of temperature, especially under a no, or little irrigation scenario, further diminishing the blue water footprint. Uncertainty in future precipitation has the greatest impact in scenarios projecting maize yield and water footprint. Our study provides hints as to how one can (i) evaluate the amount of water required to cultivate maize or other crops, and virtually traded when such crops are sold or bought, (ii) evaluate the impact of climate change upon water footprint and virtual water trade, and (iii) benchmark objectively adaptation strategies for agricultural systems with an eye on least water consumption. [Copyright &y& Elsevier]