Background: Livestock-associated meticillin-resistant Staphylococcus aureus (LA-MRSA) clonal complex (CC) 398 may be transmitted and cause morbidity and mortality in hospitals. The economic cost of stopping hospital transmission of LA-MRSA CC398 is poorly described. Early detection of transmission may limit the extent of the intervention. Aim: To evaluate core genome multi-locus sequence typing (cgMLST) for detecting transmission chains and to estimate the costs for interventions to prevent further spread after discovery of hospital transmission of LA-MRSA CC398. Methods: Five patients were involved in two episodes of transmission of LA-MRSA CC398 in a hospital. Standard interventions including MRSA screening of patients and healthcare workers were initiated. Whole genome sequences of the five isolates and 17 epidemiologically unrelated MRSA CC398 isolates from other hospitalized patients were analysed by single nucleotide polymorphism (SNP) comparisons and cgMLST. The economic costs of constraining transmission were calculated from relevant sources. Findings: The five isolates suspected to be involved in hospital transmission clustered with ≤2 SNPs in the draft genome sequences with some distance to other isolates. cgMLST allocated the five isolates to the same type, which was different from all but two of the sporadic isolates. Furthermore, cgMLST separated the five transmission isolates from all other isolates. The economic costs of the outbreak interventions exceeded €11,000 per patient. Conclusion: LA-MRSA CC398 is transmittable in hospitals, and intervention against transmission may reach considerable costs. cgMLST is useful in surveillance of hospital transmission of LA-MRSA.