Methicillin-resistant Staphylococcus aureus (MRSA) carriage and subsequent infection were prospectively compared among a well-defined group of 107 individuals infected with human immunodeficiency virus type 1 (HIV-1) who had no evidence of immune suppression and 52 epidemiologically matched, uninfected individuals. The carriage strains and infecting strains were genetically characterized. The cumulative prevalence of MRSA carriage was significantly higher among HIV-infected individuals (16.8%) than among individuals without HIV infection (5.8%) (P = .04; odds ratio, 3.3 [95% confidence interval, 1.3-14.7]). Fifteen of 21 MRSA isolates recovered from colonized individuals were identified as strain USA300. Of the 10 MRSA skin and soft tissue infections observed in this study, all occurred in HIV-infected individuals who were colonized with the same strain that caused the infection. Previous antibiotic use was the only statistically significant risk factor for MRSA carriage. These data highlight the fact that MRSA colonization and infection are important clinical issues among asymptomatic HIV-1-infected individuals.