A systematic study was carried out to investigate the distribution of 59 elements in the sediment and soil samples collected from the river Vardar (Republic of Macedonia and Greece) and its major tributaries. The samples were collected from 28 sampling sites. Analyses were performed by inductively coupled plasma-mass spectrometry. R-mode factor analysis (FA) was used to identify and characterise element associations. Seven associations of elements were determined by the method of multivariate statistics. Every factor (Factors 1-3 and 6 and 7 as geogenic and Factors 4 and 5 as anthropogenic associations of elements) are examined and explained separately. The distribution of various elements showed that there is a presence of anthropogenic elements (Ag, Cd, Cu, Ge, Pb, Sn and Zn) introduced in the river sediments and soils from the mining, metallurgical, industrial and agricultural activities in Vardar River Basin, which covers most of the Republic of Macedonia and Central-northern part of Greece.