Identifying the mode of transmission and acquisition of nosocomial pathogens is of crucial importance in designing effective surveillance and intervention for infection control in hospitals. We have used large-scale, systematic, longitudinal surveys of important multi-drug resistant (MDR) pathogens causing bloodstream infections in UK hospitals to understand the population structure of these organisms. Whole genome sequencing and phylogenetic reconstruction of these isolates allows us to accurately reconstruct the population history of these MDR pathogens across the UK and Ireland. These population histories demonstrate two clear modes of transmission: recent clonal spread within and between hospitals, and older, more diverse populations indicative of commensal spread within the wider population. Understanding these differences will enable tailored infection control procedures to minimise nosocomial acquisition of these important pathogens.