The ultrastructural effects of the lipoglycopeptide oritavancin on methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococcus (VRE) were examined by transmission electron microscopy. Oritavancin but not vancomycin induced aberrant septum formation and loss of staining of nascent septal cross walls in MRSA. Septal distortions were also observed in VRE exposed to oritavancin.