Genotyping tools for characterising nosocomial pathogens are becoming more discriminatory, efficient, and cost effective, enabling improved hospital surveillance, outbreak investigation, and infection control. We present the application of a molecular sub-typing based surveillance system for the detection and investigation of two different outbreaks of Methicillin-resistant Staphylococcus aureus (MRSA) in the neonatal intensive care and in surgical wards of a Sydney public tertiary hospital. The surveillance system includes the use of routine, prospective binary typing of MRSA to rapidly detect hospital outbreaks and to monitor changes in the molecular epidemiology. Whole genome sequencing (WGS) of MRSA was conducted to identify sub-clusters within the outbreaks detected. These analyses clarified possible links between cases where epidemiological information was limited, excluded cases from outbreaks, and identified genetic markers unique to particular outbreaks. The combination of binary typing and WGS has improved infection control practices, reduced nosocomial infections, and provided new insights into MRSA transmission in different settings in the hospital.