The 953 km long Prut River is the second largest tributary of the Danube River. It flows first in the Ukraine, then forms the border between Ukraine and Romania and then between Romania and Moldova (713 km). The objective of our investigation was to study the contribution of urban and agricultural sources of organic micropollutants in the Prut River at the Romanian-Moldavian border and in the Jijia Canal, a tributary with low dilution of wastewater from several villages (e.g. Iasi) at the Romanian site. For two sampling campaigns in November 2011 and June 2012 a target screening was performed for approximately 380 pharmaceuticals, personal care products, pesticides, biocides, additives, corrosion inhibitors, musk fragrances, and industrial chemicals using liquid chromatography followed by electrospray ionization (ESI) coupled to high resolution Orbitrap mass spectrometry [1]. In the Prut River 39 different pharmaceuticals and metabolites, 30 pesticides (including biocides) and transformation products as well as 7 household chemicals and 4 perfluoroalkyl acids totalling 80 target compounds, were determined above the LOQ. Relatively low concentrations levels were found. The highest concentrations occurred for the artificial sweetener acesulfame (750 ng/L), the pharmaceuticals metformin (240 ng/L) and 4acetamidoantipyrine (a primary metabolite of the analgesic metamizole, 210 ng/L). Concentrations of the analgesic antipyrene (phenanzone), the anti-epileptic gabapentin, and the anti-diabetic metformin were above 50 ng/L. This also applies to the household chemicals cyclamate, saccharine and caffeine. Low levels of pesticides were found (< 10 ng/L). The herbicide bentazone was determined at slightly higher concentrations (11-27 ng/L). Maximum concentrations in samples from the Jijia tributary were higher than in the Prut. The highest levels in the Jijia were determined for acesulfame (2’000 ng/L), 4-acetamidoantipyrine (500 ng/L), metformin (440 ng/L). Concentrations above 50 ng/L occurred for sucralose, cyclamate, saccharine, benzotriazole, 4,5-Methyl-1H-benzotriazole, atenolol acid, carbamazepine, carbamazepine-10,11-dihydro-10, 11-dihydroxy, diclofenac, gabapentin, metformin, sulfamethoxazole and bentazone. At Brinza, upstream of the confluence point of the Prut into the Danube, the average load of the determined compounds in the Prut River catchment amounted to 1840 kg/year. Of this total, pharmaceuticals and metabolites amounted to 685 kg/year, pesticides and transformation products to 252 kg/year and household chemicals to 903 kg/year. The highly sensitive target analysis using HRMS provided a comprehensive picture of the overall contamination pattern with polar emerging contaminants.