The Prut Riveris one of the most important rivers that cross the territory of Republic of Moldova and constitutes an important source of water supply for the country. The water quality of Prut River in Republic of Moldova is monitored monthly by the State Hydrometeorological Service. Moreover, different teams of researchers from Moldova, Romania and Ukraine are actively involved in the assessment of the water quality of Prut River based on various physicochemical parameters. One of the most common and toxic pollutants found in rivers water are heavy metals. Thus, the goal of this study was to determine the concentration of heavy metals in Prut River water and to evaluate the water quality using heavy metal pollution index (HPI) and metal index (MI). The HPI values were calculated using the formula proposed by Mohan et al. in 1996 [1], and compared with the scale used by Tiwari et al. [2]. The MI values of water samples were calculated according to Tamasi and Cini [3], and for assessment of water quality was used classification applied by Yusuf et al. [4]. In calculations were used the maximum allowable concentration for surface water regulated by the Moldovan standards [5]. Water samples were collected from the Prut River between the autumn of 2016 and winter of 2018. The sampling was carried out in Criva, Sculeni, and Cislita-Prut villages. The concentration of Mn, Cd, Pb, Hg, Ni, Cu, and Zn were monitored by applying inductively coupled plasma mass spectrometry method (ICP-MS), using a Perkin Elmer Elan DRC II ICPMS instrument. The concentrations of Mn, Cu, and Zn were found to be well below the highest permissible value for drinking water (class I of water quality) regulated by the Moldovan standards. The Pb and Hg concentrations were below the limit of detection in all samples. The concentrations of Cu corresponded to class II of water quality. The highest concentration of Cd was observed in autumn (2.2 mg/L) at sampling point in Sculeni village. In spring the concentration of this metal waselevated (class IV of water quality) throughout the entire river flow. The MI values of water samples were 0.46 near village Criva, 0.54 in Cislita-Prut village, and 0.96 in Sculeni village. Thus the water of Prut river is pure (class II) according this index. The HPI values of the samples were below the critical pollution index (100). The highest HPI (71) was observed at the sampling point in Sculeni village (high class). The HPI values for water sampled in Criva and Cislita-Prut villages indicated the medium class of heavy metal pollution.