Community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA) have emerged globally and have been associated with more severe disease than healthcare-associated MRSA (HA-MRSA). The purpose of this study was to determine whether laboratory measures of virulence can distinguish dominant CA-MRSA clones from HA-MRSA clones. We compared the production of phenol-soluble modulins (PSMs) and ability to kill Galleria mellonella caterpillars for a range of CA- and HA-MRSA strains. Twenty-two HA-MRSA strains [ST22-IV (EMRSA-15), ST36-II (EMRSA-16) and ST239-III] and 26 CA-MRSA strains [ST1-IV (PVL+ USA400), ST1-IV (PVL-), ST8-IV (USA300), ST22-IV (PVL+), ST30-IV, ST59-IV and ST80-IV] were analysed. PSM production was measured using and compared using t-tests and ANOVA. A G mellonella (caterpillar) pathogenicity model was performed, and differences were compared using survival analysis and the log-rank test. There was no significant difference in overall PSM production between HA and CA strains (P=0.090), but there was significant variation between clones (P=0.003). G. mellonella caterpillar killing varied significantly by clone (P<0.001), and overall killing was greater for HA compared with CA clones (P=0.007). The increased acute virulence phenotype of CA-MRSA clones in humans is not associated with increased PSM production in vitro or increased killing in an in vivo caterpillar pathogenicity model.