Healthcare-associated (HA) meticillin-resistant Staphylococcus aureus (MRSA) clone CC22 SCCmecIV (EMRSA-15) has recently overtaken CC30/ST36 SCCmecII (EMRSA-16) as the dominant clone in UK hospitals. CC22 SCCmecIV shows greater fitness than CC30 SCCmecII, although both are successful global pathogens. The aim of this study was to test whether mobile genetic elements (MGEs), specifically SCCmec and large plasmids encoding resistance genes, are a burden and contribute to this fitness difference. Thirty-nine clinical isolates of MRSA and meticillin-sensitive S. aureus from lineages CC30 and CC22 with a variety of antibiotic resistance genes were grown in the absence of antibiotics. A range of relative fitness measures were used to compare clinical isolates with and without SCCmecII and SCCmecIV. The same fitness measures were used to compare eight isolates with and without naturally occurring large antibiotic resistance plasmids carrying gentamicin resistance (determined by microarray) and an isolate with an introduced plasmid. Growth rate, competitive ability during co-culture and survival after desiccation were then compared. Carriage of SCCmecII contributed to the reduced fitness of CC30 MRSA. However, we found no evidence of a fitness cost due to carriage of SCCmecIV in CC22, or large antibiotic resistance plasmids in CC30 or multiple resistances in both lineages. In conclusion, many large MGEs are not a fitness burden. Surprisingly, lineage background was the most important determinant of fitness. Our results suggest CC22 SCCmecIV will remain a successful healthcare-associated clone, and resistance to meticillin and gentamicin is likely to be maintained even in the absence of antibiotic pressure.