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An innovative multi-criteria methodology was proposed for the prioritization of the Program of Measures (PoM) in the Water Region of Crete, and applied specifically to the basin of Geropotamos river according to the requirements of the Water Framework Directive. This study relied on the four pillars of sustainability and the EU cross-compliance legislative objective for the minimization of the climate change impact. The multi-criteria evaluation methodology was based on the results of four different types of analyses: a DPSIR analysis, a SWOT analysis, a Cost-Benefit Analysis and a climate change impacts analysis. Public participation on the results of the study with local stakeholders was used at every stage of the multi-criteria evaluation process, from the selection and weighing of the criteria to the final ranking and measures' prioritization. The PoM contains two types of measures: basic measures which deal with the implementation of existing legislation and are the same for all regions of Greece and additional measures which are specified for the Region of Crete. The results of the prioritization process in Geropotamos Basin suggests that improving the water quality and ecological status of available water resources do not always require significant financial resources and can have a high impact in terms of achieving "good" quality status. (C) 2019 Elsevier B.V. All rights reserved.