The aim of this work is to define harmonized reference conditions and assessment thresholds for selected criteria elements of the Marine Strategy Framework Directive (MSFD) Descriptor 5 (Eutrophication) in the Eastern Mediterranean Sea and to test if a tool for integrated assessment of the status of marine systems can be used as a common methodological approach. In this frame, we tested two statistical approaches in order to set threshold values for four criteria of Descriptor 5: nutrients, chlorophyll a, transparency and dissolved oxygen in the bottom waters. It is noteworthy that this work revealed the need to apply common procedures in data treatment and assessment evaluation. This is the first attempt to set common methods for the assessment of eutrophication in the Eastern Mediterranean, which is essential in marine environments, especially those shared by several countries. To this end, we have applied common criteria and metrics and established thresholds "Good" and "Moderate" for nutrients, chlorophyll a, transparency and dissolved oxygen in the bottom waters for the different Water Types of the Adriatic and Aegean Seas (I, II, IIIW, IIIE), based on datasets provided by Italy, Slovenia, Croatia and Greece. The selected criteria elements were common for all countries, providing a unified approach to GES assessment of two case study areas: the Adriatic Sea and the Saronikos Gulf. Dissolved Inorganic Nitrogen (DIN) threshold values of 15.6, 6.85, 1.61 and 2.11 μmol L-1 were set for the Water Types I, II, IIIW and IIIE, respectively. We also tested if an aggregation tool for GES assessment, such as Nested Environmental status Assessment Tool (NEAT), could be used as a common methodological approach. The comparison of NEAT with TRIX showed good comparability. In this end, NEAT can be used as a useful and much needed assessment tool for assessing eutrophication status of the marine.