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Developing adaptation strategies in Vitis vinifera, a crop sensitive to climate change, is crucial for resilience of traditional viticultural systems, especially in climate-vulnerable areas like the Mediterranean basin. A progressive warming is demonstrated to alter the geographical distribution of grapevine, reducing land capability for typical grapes and vine productions in most Southern European districts traditionally specialized in tree crops. Grapevine growth and reproduction under climate change require a continuous monitoring to adapt agronomic practices and strategies to global change. The present study illustrates an empirical approach grounded on a set of bio-physical indicators assessing the genotype-related response to climate variation. This approach was tested in Umbria, central Italy, to verify the response of some major international and local grapevine varieties to climate variation during a relatively long time interval (1995-2015). Long-term data for ripening time and berry quality collected in the study area were correlated to representative bioclimatic indices including Winkler, Huglin, and Cool night indicators. Results of this study highlighted the increase of air temperature (reflecting the inherent growth in thermal availability for maturation) and the alteration of precipitation patterns toward more intense precipitation. Climate variability exerted distinctive impacts on grapevine phenology depending on the related genotype. Empirical findings underline the usefulness of a permanent field monitoring of the relationship between selected climate variables and grape ripening with the aim to develop adaptive viticultural practices at farm's scale.