Climate change is one of the most serious challenges facing mankind in the 21st century. Extreme climatic events are expected to be more frequent and severe leading to various natural disasters. Vietnam, with more than 70% of the population working in agriculture and having a high density of inhabitants on the coastal plains, is one among those countries heavily impacted by climate change. The aim of this paper is to present a methodology to assess the impacts of climate change on a flood prone area of a coastal river basin in the central region of Vietnam. The hydrological simulations are based on a validated deterministic hydrological model MIKE SHE, which integrates geology, soil, topography, river systems and climate variables. The present-day climate, over the period of 1991–2010, was reasonably simulated by the hydrological model. Future climate (2091–2100) information was obtained from a dynamical downscaling of the global climate models, CCSM3.0, MIROC-medres and ECHAM5 under A2 scenario, using the Regional Climate Model: Weather Research and Forecasting Model. The result indicates that with this area, the ensemble future river flow under scenario A2 might increase up to 200% during rainy season and reduce to roughly 7–30% during dry season. The study also analyzed the changes in the flood dynamics of the study region, the hydrological shift and the uncertainties of climate change simulation. This paper showcases an operational approach to integrate the results from the impacts of climate change to flood protection measures that would help in devising resilience strategies. [ABSTRACT FROM AUTHOR]