Every year, between 165,000 and 200,000 Australians contract a healthcare-associated infection (HAI), causing significant ill health and costs to the health system. Furthermore, the impact of these infections is exacerbated by rapidly increasing rates of antibiotic resistance. Currently, there is limited laboratory capacity to track pathogens causing these infections in real-time or to detect cross-transmission events. However, low cost, whole genome sequencing (WGS) promises to revolutionise modern clinical microbiology by capturing the entire bacterial genome, providing unparalleled understanding of clinically relevant characteristics and transmission dynamics. Here, we established a pre-emptive WGS-based surveillance program to identify clustering of clinically relevant multi-resistant bacteria, suggesting in-hospital transmission, before an outbreak is established or recognised. Over a one year period (January 2018 to March 2019) more than 1000 multidrug-resistant bacterial isolates, specifically ESBL-producing Enterobacteriaceae, methicillin- resistance S. aureus (MRSA) and vancomycin-resistance enterococci (VRE), were collected from patients admitted to three metropolitan Brisbane hospitals, sequenced and subjected to genomic analysis. Core genome SNP data, used to establish the relationship between isolated and detect in-hospital transmission events, identified 28 distinct clusters (>2 isolates) of closely related isolates that were not identifiable using traditional surveillance techniques. Of these 28 clusters, 11 were contained to one of three target hospitals. The remaining 17 clusters represent inter-hospital transmission events or community outbreak strains acquired prior to hospital admission. Additional targeted environmental sequencing (isolate and metagenomics) of three clusters identified environmental reservoirs within the hospital as an important source of outbreaks of multi-drug resistant organisms. Overall, this work demonstrates that routine WGS surveillance is an effective tool to enhance and support established infection control responses. The single nucleotide resolution offered by WGS enables transmission pathways between patients and hospital environments to be delineated at the highest possible resolution and is essential for identifying missed outbreaks and excluding misidentified outbreaks, which can inappropriately trigger infection control responses.