The efficacy and safety of telavancin is under evaluation for the treatment of subjects with complicated Staphylococcus aureus bacteremia and S. aureus right-sided infective endocarditis. This study evaluated the telavancin activity against a global collection of S. aureus causing bloodstream infections (BSI), including endocarditis, to support the development of bacteremia/endocarditis clinical indications. This study included a total of 4191 S. aureus [1490 methicillin-resistant S. aureus (MRSA)], which were unique (one per patient) clinical isolates recovered from blood samples collected during 2011-2014 in a global network of hospitals. All isolates were deemed responsible for BSI, including endocarditis, by local guidelines. Isolates were tested for susceptibility by broth microdilution. Telavancin (MIC50/90, 0.03/0.06 μg/ml) inhibited all S. aureus at ≤0.12 μg/ml, the breakpoint for susceptibility. Equivalent minimum inhibitory concentration (MIC) values (MIC50/90, 0.03/0.06 μg/ml) were obtained for telavancin against methicillin-susceptible S. aureus (MSSA) and MRSA isolates, as well as MRSA from community and healthcare origins. Similar telavancin activities (MIC50, 0.03 μg/ml) were observed against MRSA subsets from North America and Europe, while isolates from the Asia-Pacific (APAC) and Latin America regions had MIC50 values of 0.06 μg/ml. MRSA with vancomycin MIC values of 2-4 μg/ml and the multidrug resistance (MDR) subset had telavancin MIC50 results of 0.06 μg/ml, although the MIC100 result obtained against these subsets remained identical to those of MSSA (MIC100, 0.12 μg/ml, respectively). This study updates the telavancin in vitro activity, which continues to demonstrate great potency against invasive S. aureus, regardless of the susceptibility phenotype or demographic characteristics (100.0% susceptible), and supports the sought-after subsequent indications.