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This study is focussed on a comprehensive investigation on the state of pollution of Danube and Sava rivers in Belgrade region. Different complementary analytical approaches have been used covering both (i) organic ccontaminants in river water by target analyses of hormones and neonicotinoids as well as non-target screening analyses and (ii) heavy metals in sediments. Finally, some common water quality parameters have been analysed. The overall state of pollution is on a moderate level. Bulk parameters did not reveal any unusual observation. Also quantification of preselected organic contaminants did not point to elevated pollution. A more significant contamination was measured for chromium, nickel, zinc and partially copper in sediments with values above target values according to Serbian regulations. Lastly, non-target screening analysis revealed a wider spectrum of organic contaminants comprising pharmaceuticals, technical additives, personal care products and pesticides. The study presented a comprehensive view on the state of pollution of Sava and Danube rivers and is the base for setting up further monitoring programs. As a superior outcome it has been illustrated how different chemical analyses can point to different assessments of the river quality. The comparison of target and non-target analyses pointed to potential misinterpretation of the real state of pollution.