We describe 279 hospitalized Canadian aboriginals in whom methicillin-resistant Staphylococcus aureus (MRSA) was detected. They were identified in 38 Canadian hospitals from 1995 through 2002. Compared with nonaboriginals, aboriginals were more likely to be younger than 18 years of age (OR, 1.8; P<.0001), to have had an MRSA infection (OR, 3.8; P<.0001), and to have had MRSA isolated from specimens of skin or soft tissue (OR, 4.1; P=.016). The clinical features of MRSA infection in aboriginals are distinct from those in the general patient population with MRSA infection in Canadian hospitals, and the genetic background of MRSA isolates from aboriginals also varies from that of strains from the non-aboriginal population.