Following multiannual studies conducted on Dniester and Prut Rivers on ichtyofauna (within the territorial limits of the Republic of Moldova), it became possible to elucidate the comparative aspects between these two large aquatic macroecosystems. Although the basin of the Danube (of which Prut River belongs) and Dniester River are separated by the geographical barrier, their ichtyofauna has many common points. The great similarity is due to the shallow continental platform between the mouths of the Danube and the Dniester valley, which shows that, during the glacial periods, the Dniester was a tributary of the lower Paleo-Danube. Despite this, the hydrobiotopic characteristics and the special anthropogenic threats have revealed some distinctive ichtyofaunistic particularities: • According to the diversity and the proportion of fish species with various rarity status, Dniester River has more significant values han the Prut River (Vimba vimba, Ballerus sapa, Pelecus cultratus, Leuciscus Leuciscus idus, Alburnoides bipunctatus, Barbus petenyi, Sabanejewia aurata, Sabanejewia bulgarica, Lota lota, Zingel zingel, Zingel streber, etc.), which indicates a higher anthropic pressure on these river ecosystem. • Representatives of genus Romanogobio, Gobio, Sabanejewia, Gymnocephalus, are more common in catches in the Prut River (except the Gymnocephalus acerina missing in the river), and representatives of Cobitis sp. which hold a higher constancy in Dniester River. • Migratory Clupeidae (Alosa immaculata, Alosa tanaica, Clupeonella cultriventris) are better represented in Dniester River (except Alosa tanaica, which migrates massively on the route: Black Sea → Danube → Lower Prut → Beleu Lake). • Among semi-migratory species of fish, it is noted that the Pelecus cultratus is endangered in the Dniester River, while in the Prut River this species shows a positive dynamics of the herds. Rutilus frisii, in Dniester River, has formed two growing populations, while in Prut River the species is missing. • The quantitative values of the intervenient fish species (such as Gobiidae species, Syngnathus abaster, Gasterosteus aculeatus, Pungitius platygaster, Clupeonella cultriventris, Atherina boyeri, etc.,) in Dniester River are much higher than in the Prut River. • The greater abundance of the oxyphilous Gymnocephalus cernua from the Stinca-Costeşti reservoir, including some reophilous fish species like the Barbus barbus, Vimba vimba, Squalius cephalus, Ballerus sapa, Gobio and Romanogobio species, etc., implies a more favorable ecological status compared to the Dubăsari accumulation. Acknowledgement: The study was performed within the projects: 15.817.02.27A -AQUASYS, 18.51.07.08A/PS, BSB 027 MONITOX, BSB 165 HYDROECONEX, MIS ETC 1676, MIS ETC 1150.