The main objective of this paper is to provide data on the Danube River Delta Biosphere (Romania) aquatic ecosystem quality and Vardar – Axios River Valley (FYR Macedonia – Greece) on comparison basis from on the long-term analytical investigation for specific indicators. In particular this paper is focused on the quality assessment of surface water, sediment and biota of the Danube Delta Biosphere Reservation. Information is presented on water and sediment quality variations in heavy metals over a seven-year period (2003 and 2009), from April to October. Samples have been collected monthly from two different locations (Murghiol and Uzlina) situated on St. Gheorghe branch. The presence of some toxic metals was noticed in surface waters and sediments. In both locations in different periods of time high concentrations of Fe, Mn, heptachlor, Lindane, PCBs, phenols, mineral oil in surface water represent an acute problem for the inhabitants of the Danube Delta which use water for household consumption directly from the Danube, without any treatment. This presents a series of disadvantages, such as a high risk of disease for the population, mostly for children and old people. The evolution of the pollution levels of Danube waters was compared with that of Axios / Vardar River, another major trans-boundary river in the Balkan area.