Remnants of native riparian vegetation on the floodplain of the Hawkesbury–Nepean River near Sydney, have significant conservation value, but contain a large component of weeds (i.e. exotic species that have become naturalized). A proposal for the introduction of environmental flows required an assessment of potential impacts on 242 native and 128 exotic species recorded along 215 km of the river. The likely effects of frequency, season, depth and duration of inundation were considered in relation to habitat, dispersal season and tolerance to waterlogging. Overseas studies provided only limited information applicable to the study area; however, comparisons with similarly highly modified riparian habitats in New Zealand were instructive. Depth and season of inundation appear to be the variables with the greatest potential for differential effects on weeds and native plants. Because of likely spread of propagules and enhancement of growth under the present nutrient-enriched conditions, environmental flows that would cause more frequent flooding to higher levels of the riparian zone were judged to be of more benefit to weed species than native species, unless supported by bushland management including weeding. Predictions were limited by incomplete data on Hawkesbury–Nepean species, but two types of environmental flow were judged to be potentially beneficial for native water-edge plants, and worth testing and monitoring: first, flows that maintain continuous low-level flow in the river, and second, higher level environmental flows restricted to the river-edge habitat in autumn (the season in which a greater proportion of native species than weed species are known to disperse propagules). In summary, the presence of environmental weeds in riparian vegetation constrain the potential for environmental flows to improve river health. However, with ongoing monitoring, careful choice of water level and season of flow may lead to environmental flows that add to our knowledge, and benefit riparian vegetation along with other river system components.