The Iberá region is the second largest wetland in the world and hosts hundreds of plants and animal species. Water availability in the region is the result of the balance between precipitation, evapotranspiration and runoff, and the region is highly sensitive to changes in this balance. In this paper the VIC hydrologic distributed model is calibrated over the Iberá region using observed temperature, precipitation and surface wind data. This study also examines the ability of the RCA3-E regional climate model to simulate the present climate and the skill of VIC to represent the hydrologic cycle of the wetland when forced by RCA3-E output data. It was found that errors in the climate model significantly affect hydrological simulations and this can be improve if a correction scheme for systematic errors is applied. Finally, in order to determine a potential future scenario of water availability in the Iberá region, the hydrologic model is forced with simulations provided by the RCA3-E by the end of the present century for an intermediate greenhouse gases emissions scenario after correcting the identified systematic errors. The results show that, although the regional climate model projects an increase in both precipitation and mean temperature, rainfall changes could compensate the rise in evapotranspiration given the increase in temperatures and this would lead to larger streamflows of the Iberá region’s main river.