Background: Increasingly frequent reports of vancomycin treatment failures for serious methicillin-resistant Staphylococcus aureus (MRSA) infections provide impetus for comparative in vitro studies to assess the activity of newer antimicrobial agents against a range of MRSA isolates. Methods: A sample of 168 MRSA derived from a long-term MRSA collection was subjected to susceptibility testing to telavancin, daptomycin, linezolid, tigecycline and vancomycin by broth micro-dilution. Data were reviewed for sporadic occurrence of isolates with reduced susceptibility. Analyses were performed to test for temporal trends toward decreasing susceptibility and to compare susceptibility of isolates from different infection sites. Results: No MRSA isolate from any time period was resistant to test antibiotics. For daptomycin, linezolid and tigecycline, there were no susceptibility differences between the pre- and postclinical availability periods. All newer agents here active against MRSA isolates with minimum inhibitory concentrations (MICs) of vancomycin >1 mg/l, but there were significant correlations in susceptibility among several pairs of antibiotics. Conclusions: Telavancin and other newer antistaphylococcal agents were fully active against MRSA from various infection sites including isolates with vancomycin MIC >1 mg/l.