We describe clinical and laboratory characteristics of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections with vancomycin MICs of 2 μg/ml and compare heteroresistant-intermediate S. aureus (hVISA) to non-hVISA. Health care-associated community-onset infections were the most common and resulted in frequent complications and relapses. hVISA-infected patients were more likely to have been hospitalized in the year prior to MRSA culture.