SUMMARYST131 Escherichia coli is an emergent clonal group that has achieved successful worldwide spread through a combination of virulence and antimicrobial resistance. Our aim was to develop a mathematical model, based on current knowledge of the epidemiology of ESBL-producing and non-ESBL-producing ST131 E. coli, to provide a framework enabling a better understanding of its spread within the community, in hospitals and long-term care facilities, and the potential impact of specific interventions on the rates of infection. A model belonging to the SEIS (Susceptible–Exposed–Infected–Susceptible) class of compartmental models, with specific modifications, was developed. Quantification of the model is based on the law of mass preservation, which helps determine the relationships between flows of individuals and different compartments. Quantification is deterministic or probabilistic depending on subpopulation size. The assumptions for the model are based on several developed epidemiological studies. Based on the assumptions of the model, an intervention capable of sustaining a 25% reduction in person-to-person transmission shows a significant reduction in the rate of infections caused by ST131; the impact is higher for non-ESBL-producing ST131 isolates than for ESBL producers. On the other hand, an isolated intervention reducing exposure to antimicrobial agents has much more limited impact on the rate of ST131 infection. Our results suggest that interventions achieving a continuous reduction in the transmission of ST131 in households, nursing homes and hospitals offer the best chance of reducing the burden of the infections caused by these isolates.