Lake Vänern and River Göta älv in southern Sweden constitute a large and complex hydrological system that is highly vulnerable to climate change. In this study, an ensemble of 12 regional climate projections is used to simulate the inflow to Lake Vänern by the HBV hydrological model. By using distribution based scaling of the climate model output, all projections can accurately reproduce the annual cycle of mean monthly inflows for the period 1961–1990 as simulated using HBV with observed temperature and precipitation (‘HBVobs’). Significant changes towards higher winter inflow and a reduced spring flood were found when comparing the period 1991–2008 to 1961–1990 in the HBVobs simulations and the ability of the regional projections to reproduce these changes varied. The main uncertainties in the projections for 1991–2008 were found to originate from the global climate model used, including its initialization, and in one case, the emissions scenario, whereas the regional climate model used and its resolution showed a smaller influence. The projections that most accurately reproduce the recent change suggest that the current trends in the winter and spring inflows will continue over the period 2009–2030.