Gram-positive pathogens isolated in 15 Canadian hospital laboratories between 2011 and 2013 were tested for susceptibility to oritavancin and comparative antimicrobial agents using the Clinical and Laboratory Standards Institute broth microdilution method. Oritavancin demonstrated in vitro activity equivalent to, or more potent than, vancomycin, daptomycin, linezolid, and tigecycline against the isolates of methicillin-susceptible Staphylococcus aureus (n=1460; oritavancin MIC 90 , 0.06μg/mL; 99.7% oritavancin-susceptible), methicillin-resistant S. aureus (n=427; oritavancin MIC 90 , 0.06μg/mL; 99.5% oritavancin-susceptible), Streptococcus pyogenes (n=132; oritavancin MIC 90 , 0.25μg/mL; 99.2% oritavancin-susceptible), Streptococcus agalactiae (n=156; oritavancin MIC 90 , 0.12μg/mL; 100% oritavancin-susceptible), and Enterococcus faecalis (n=304; oritavancin MIC 90 , 0.06μg/mL; 98.7% oritavancin-susceptible) tested.