Study region: This study focuses on a mountainous region experiencing urban sprawl and growing irrigation needs: the canton of Vaud (Switzerland). Study focus: Switzerland’s description as Europe’s water tower might evolve by the end of the century, as it should undergo significant hydro-climatic changes. Focusing on Western Switzerland is all the more important because a large part of the Swiss population lives in this area and because this region experienced water shortage episodes during the last decade. Climate change and its impacts on seasonal water resources availability and hydrological regimes were explored for the medium term (2050–2071). Flows were simulated based on a daily semi-distributed hydrological model. A calibration and corroboration procedure was performed over the 1984–2005 period. Future changes were derived from Swiss climate scenarios that rely on ten regional climate models. New hydrological insights for the region: By the 2060 horizon, the increase in temperature causes a higher ratio of liquid precipitation and a decrease in snow accumulation during winter. These variations give rise to earlier high flow peaks and more severe low flows. Hydrological regimes evolve and rivers become characterized by a pluvial regime. These seasonal hydro-climatic changes are of prior importance in an area where urbanization and irrigation keep increasing: the question arises on the capacity of water resources to meet future water demands.