Randomized trials supporting the benefit of endovascular treatment in acute ischemic stroke patients with a large early infarction are not yet available. Few retrospective studies exist that suggest a potential positive treatment effect on functional outcome, as well as procedural safety. However, potential benefit or harm of MT in patients with low initial ASPECTS is still a subject of current debate, and in particular, how to select these patients for treatment. The purpose of this pilot study was to evaluate how early tissue water uptake in acute ischemic brain might determine lesion fate and functional outcome in low ASPECTS patients undergoing MT. We observed that the degree of early water uptake measured by quantitative NWU was significantly associated with functional outcome in low ASPECTS patients, yielding a higher diagnostic power compared to other parameters such as ASPECTS, age, or NIHSS. No conclusive evidence of a beneficial effect of successful reperfusion was observed in patients with low ASPECTS and high NWU, which highlights the potential of NWU as a tool to specify patient selection.