OBJECTIVES: To develop a system dynamics model with a stochastic component to analyse the cost-effectiveness of bacterial whole-genome sequencing (WGS) versus current typing methods to detect and monitor outbreaks of methicillin-resistant Staphylococcus aureus (MRSA) in the UK National Health Service (NHS). METHODS: The model, developed in R, simulated a low-risk ward and a high-risk ward (e.g. an intensive care unit). Patients were assumed to move between three states: susceptible, colonised, or infected (symptomatic). Healthcare workers were either uncontaminated or MRSA-colonised. Clinical inputs were identified from peer-reviewed primary research papers, systematic reviews, published models, data published by the NHS and from clinical experts. Relevant costs were identified from the Department of Health guidelines on MRSA infection management, and other published sources. The zero tolerance MRSA policy set by NHS England, which includes financial sanctions, was implemented in the model. RESULTS: Over a one-year time horizon, although prevalence was higher on the high-risk ward, outbreaks occurred most frequently on the low-risk ward due to the higher number of patients. Preliminary results indicate that fewer outbreaks were declared when using WGS to identify the MRSA strain compared to current methods, due to the increased sensitivity of WGS in identifying unrelated MRSA strains and therefore classifying fewer concurrent colonisations/infections as ‘outbreaks’. Fewer outbreaks resulted in cost-savings due mainly to a lower cost of fines, and therefore WGS is likely to be cost-effective where the technology and infrastructure is available. CONCLUSIONS: This newly developed model is the first formal attempt to evaluate the cost-effectiveness of WGS for detecting and monitoring outbreaks of MRSA. Initial results indicate that WGS will be cost-effective due to fewer outbreaks being declared. Further planned developments include expanding the model to simulate a complete hospital, as well as including start-up costs of setting up WGS services.