Following the recent reform of the Community aid scheme, improving competitiveness by reducing production costs is crucial to guaranteeing the sustainability of the cotton sector (including farms, upstream and downstream industries). Some authors have suggested that the introduction of genetically modified (GM) varieties of cotton with tolerance to insect pests would be a key element of a cost reduction strategy. The potential introduction of GM cotton in the European Union (EU) makes it necessary to study the possible situations that might arise due to the coexistence of GM and conventional crops. This paper studies how GM and conventional cotton (for both seed and fibre production) can coexist in the same region/landscape while minimising the possible levels of adventitious GM presence in non-GM cotton by adapting current agricultural practices. The Andalusia region (Southern Spain) is used as a case study. About 92 475 hectares of cotton were grown during the 2003/2004 seasons. Using information from expert panels, a literature review, a dedicated farmers’ survey and a probabilistic model, the possible sources of adventitious GM cotton presence in non-GM cotton are identified. The probabilistic model is used to estimate the maximum levels of adventitious admixture and the probability for this admixture to occur. Agricultural practices adapted to different coexistence scenarios are proposed and an economic assessment is carried out to estimate the impact on the GM grower’s gross margin.