Climex® climate-matching and inferential-modelling was used to examine the naturalisation potential of genetically modified and non-transgenic Upland Cotton (Gossypium hirsutum variety hirsutum) in Australia north of latitude 22°S. The Climate-Match (CM) function was used to identify locations in north-east Australia where climate matches (CM Index > 0.7) the experimental sites of Eastick [Eastick, R., 2002. The Potential Weediness of Transgenic Cotton in Northern Australia. Northern Territory Department of Business, Industry and Resource Development Technical Bulletin No. 305 (Internet resource: http://cotton.pi.csiro.au/Assets/PDFFiles/TB3051.pdf)] in north-west Australia. Most of Australia north of 22°S had climate matching one or more of the sites of Eastick (2002), locations where cotton is highly unlikely to naturalise. Climex inferential models were developed using parameter values derived from the GOSSYM and OZCOT simulation models and validated against the documented distributions of (a) Indigenous G. hirsutum in Central America, (b) where it is naturalised in West Africa, and (c) Upland Cotton in West Africa. The climate-based predictions of potential distribution in Australia indicated that cotton has naturalisation potential only in the coastal regions of north-east Australia. The rest of Australia was either too cold, too dry, or both. These predictions were further refined through overlay of soil-nutrient and existing land-use data. The overlay of soil nutrient data further restricted the most suitable areas to coastal north-east Australia primarily in the wet tropics between latitudes 16°S and 19°S. Consideration of existing land-use patterns indicated that the probability of naturalisation in these potentially suitable areas was very low because these areas currently have either existing forests, or are used for managed agricultural systems, principally sugarcane. Competition from a suite of aggressive tropical weeds further reduced naturalisation potential. In less intensively managed and seasonally dry areas, fire was considered a major limitation to naturalisation of cotton. The Weed Risk Assessment (WRA) protocol, used by Biosecurity Australia to evaluate new plant importations into Australia, was used to produce an overall assessment of the weediness risk for non-transgenic, Bollgard II® and Roundup Ready® Flex cottons in north-east Australia. Because neither the Bollgard II® nor the Roundup Ready® characters conferred any advantage in the north-east Australia environment, the transgenic status of the plant did not alter the naturalisation potential or weediness risk. The WRA score of cotton in north-east Australia (-5) indicates that it has essentially zero risk of establishing as a weed in this area, especially when compared to WRA scores of other major crop plants and the competing weed species.