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Moderate to large earthquakes can increase the amount of water feeding stream flows, mobilizing excess water from deep groundwater, shallow groundwater, or the vadose zone. Here we examine the regional pattern of streamflow response to the Maule M8.8 earthquake across Chile’s diverse topographic and hydro-climatic gradients. We combine streamflow analyses with groundwater flow modeling and a random forest classifier, and find that, after the earthquake, at least 85 streams had a change in flow. Discharge mostly increased (n = 78) shortly after the earthquake, liberating an excess water volume of >1.1 km(3), which is the largest ever reported following an earthquake. Several catchments had increased discharge of >50 mm, locally exceeding seasonal streamflow discharge under undisturbed conditions. Our modeling results favor enhanced vertical permeability induced by dynamic strain as the most probable process explaining the observed changes at the regional scale. Supporting this interpretation, our random forest classification identifies peak ground velocity and elevation extremes as most important for predicting, streamflow response. Given the mean recurrence interval of similar to 25 yr for >M8.0 earthquakes along the Peru-Chile Trench, our observations highlight the role of earthquakes in the regional water cycle, especially in arid environments. (C) 2016 Elsevier B.V. All rights reserved.