Meticillin-resistant Staphylococcus aureus (MRSA) USA300 clone is commonly found in the community and is being increasingly reported in the healthcare setting. A retrospective analysis was conducted to compare the epidemiology and outcomes between community-associated (CA) and healthcare-associated (HA) USA300 MRSA infections. The study enrolled 160 subjects with USA300 MRSA infections (47.5% CA-MRSA and 52.5% HA-MRSA). Failure in the HA group was higher (38.1%) compared with the CA group (23.7%) (P=0.05). Predictors of failure included male gender, age, presence of any co-morbidity, coronary artery disease, chronic kidney disease, history of MRSA, previous admission, fluoroquinolone exposure, HA infection and osteomyelitis (P<0.05). Independent predictors of failure were osteomyelitis, history of MRSA, male gender and pneumonia. Recurrent disease was found in 32.6% of cases. Overall, USA300 MRSA most commonly causes infection of the skin and skin structure, however, ca. 20% of subjects can experience more invasive disease with infection of the bloodstream, lung or bone. Failure rates are higher in subjects with healthcare risk factors or if the infection was acquired in the hospital, with these subjects experiencing more invasive infections such as bacteraemia, pneumonia or osteomyelitis.