ABSTRACT. This study investigates the evolution of Greenland ice sheet flux focusing on five of the main fast flowing regions (Petermann glacier, North East Greenland Ice Stream, Kangerdlugssuaq glacier, Helheim glacier and Jakobshavn glacier) in response to 20th and 21st century climate change. A hybrid (shallow ice and shallow shelf) ice-sheet model (ISM) is forced with the combined outputs of a set of seven CMIP5 models and the regional climate model MAR. The ISM simulates the present-day ice velocity pattern, topography and surface mass balance (SMB) in good agreement with observations. Except for the Kangerdlugssuaq glacier, over the 21st century all the fast-flowing areas have exhibited a decrease in ice flux as a result of a negative SMB rather than dynamical changes. Only the fronts of Kangerdlugssuaq and Helheim glaciers have shown an interannual variability driven by dynamical rather than climate changes. Finally, the results predict a substantial inland ice margin retreat by the end of the 21st century, especially along the northern coasts.