Genome sequencing has provided snapshots of the transmission of methicillin-resistant Staphylococcus aureus (MRSA) during suspected outbreaks in isolated hospital wards. Scale-up to populations is now required to establish the full potential of this technology for surveillance. We prospectively identified all individuals over a 12-month period who had at least one MRSA-positive sample processed by a routine diagnostic microbiology laboratory in the East of England, which received samples from three hospitals and 75 general practitioner (GP) practices. We sequenced at least 1 MRSA isolate from 1465 individuals (2282 MRSA isolates) and recorded epidemiological data. An integrated epidemiological and phylogenetic analysis revealed 173 transmission clusters containing between 2 and 44 cases and involving 598 people (40.8%). Of these, 118 clusters (371 people) involved hospital contacts alone, 27 clusters (72 people) involved community contacts alone, and 28 clusters (157 people) had both types of contact. Community- and hospital-associated MRSA lineages were equally capable of transmission in the community, with instances of spread in households, long-term care facilities, and GP practices. Our study provides a comprehensive picture of MRSA transmission in a sampled population of 1465 people and suggests the need to review existing infection control policy and practice.This work was supported by grants from the UK Clinical Research Collaboration Translational Infection Research Initiative and the Medical Research Council (grant no. G1000803) with contributions to the grant from the Biotechnology and Biological Sciences Research Council, the National Institute for Health Research (NIHR) on behalf of the Department of Health, and the Chief Scientist Office of the Scottish Government Health Directorate (to S.J.P.); by a Hospital Infection Society Major Research Grant; by Wellcome Trust grant no. 098051 awarded to the Wellcome Trust Sanger Institute; and by Wellcome Trust 201344/Z/16/Z awarded to F.C. M.S.T. is a Wellcome Trust Clinical PhD fellow. M.E.T. is a Clinician Scientist Fellow, supported by the Academy of Medical Sciences and the Health Foundation and by the NIHR Cambridge Biomedical Research Centr