Glaciers of the central Andes have recently been retreating response to global warming, with large consequences on the hydrological. regime. We assessed here potential climate change impacts until 2100 upon the hydrologic regime of the largely snow-ice melt driven Maipo River basin (closed at El Manzano, ca. 4800 km(2)), watering 7 M people in the metropolitan region of Santiago de Chile. First, a weather-driven hydrological model including simplified glaciers' cover dynamics was set up and validated, to depict the hydrological regime of this area. In situ data from recent glaciological expeditions, ice thickness estimates, historical weather and hydrological data, and remote sensing data including precipitation from the Tropical Rainfall Measuring Mission (TRMM), and snow cover and temperature from the Moderate Resolution Imaging Spectroradiometer (MODIS) were used for model set up. We subsequently forced the model with projections of temperatures and precipitations (plus downscaling) until 2100 from the GCM model ECHAM6, according to 3 different radiative concentration pathways (RCPs 2.6, 4.5, 8.5) adopted by the IPCC in its AB5. We investigated yearly and seasonal trends of precipitation, temperature and hydrological fluxes until 2100 under the different scenarios, in projection period (PR, 2014-2100), and we compared them against historically observed trends in control period (CP, 1980-2013). The results show potential significant increasing trends in temperature until 2100, consistently with observed historical trends, unless for Spring (OND). Precipitation varies more uncertainly, with no historically significant changes, and only few scenarios projecting significant variations. In the PR period, yearly flow decreases, significantly under RCP8.5 (-0.31 m(3)s(-1)). Flow decrease is expected especially in Summer (JEM) under RCP8.5 (-0.55 m(3)s(-1)). Fall (AMJ) flows would decrease slightly, while winter (JAS) flows are projected to increase, and significantly under RCP4.5 (+0.22 m(3)s(-1)), as due to sustained melting therein. Spring (OND) flows also would decrease largely under RCP8.5, down to -0.67 m(3)s(-1), due to increased evapotranspiration for high temperatures.