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An assessment is carried out of future changes in the agroclimatic conditions and crop productivity of spring wheat across the major grain-growing regions of European Russia. Calculations are conducted using a crop model driven by high-resolution, multiple realization regional climate change simulations under the IPCC RCP8.5 scenario. It has been shown that this scenario can lead to a future decrease in the yield of spring wheat by 9.1 ± 2.3% (2030–2039), 10.3 ± 3.2% (2050–2059), and 18.9 ± 2.8% (2090–2099) as compared with the yield at the end of XX century. In the southeastern part of the region, where there are major spring wheat areas, the projected yield change is expected to be –6.7 ± 3.0% by 2050–2059 and −21.5 ± 3.1% by 2090–2099. Fertile lands in the Central Black-Earth region (southwest of Moscow) will suffer even more due to a significant increase in the aridity and decrease of the growing season. There the projected drop in yield is simulated to be 15.8 ± 5.1% by 2050–2059 and 32.9 ± 3.4% by 2090–2099. However, the major losses in total production (gross yield) are expected to occur in the Privolzhsky Federal District where the spring wheat areas amount to 87% of the total cultivated area in the region.