Climate variables such as temperature, insolation, and precipitation directly affect production as well as the quality of wine. This article simulates the climatic conditions of the Protected Designation of Origin (PDO) Sierra de Salamanca in 2050, in order to delimit the potential areas for the cultivation of Vitis vinifera, and thus, adapt the current vineyards in addition to developing new vineyards in potential areas with suitable varieties. The 2050 climatic conditions were calculated from the study of different bioclimatic indexes including the Growing season suitability (GSS), Growing season precipitation (GSP), Degree-days of Winkler and Amerie (Winkler Index), and Huglin Index (HI), etc. from 1950 to 2018. Based on the trends observed from each index, continuous maps were developed by the interpolation of the inverse of the distance to classify the area bioclimatically. These indices were later extrapolated and analysed in order to biographically map the PDO in the year 2050, dividing the study area into three zones for the cultivation of the vineyard: very favourable, favourable, and appropriate. This study proved that in the next 30 years, temperature will increase and rainfall will decrease in the PDO Sierra de Salamanca, causing a 75% reduction in the very favourable area for the cultivation of the vineyard. The favourable area will be reduced by half while the appropriate area will increase by four times its current size.