Background: Methicillin-resistant Staphylococcus aureus (MRSA) is increasingly recognized as a threat for people living with HIV/AIDS (PLWHA). However, the magnitude of asymptomatic MRSA colonization in that group varies among different countries and geographic regions. Methods: We conducted a study that aimed at identifying the prevalence, risk factors and spatial epidemiology of both overall S. aureus and MRSA colonization among PLWHA from small cities from inner São Paulo State, Brazil. MRSA isolates were characterized using Pulsed-Field Gel Electrophoresis (PFGE), and submitted to typing of the Staphylococcal Chromosome Cassete (SCC)mec. Spatial analysis was performed to search for geographical clusters and correlation with socioeconomic indicators. Results: In a first point prevalence survey, nasal and oropharyngeal swabs of 368 people were collected. Sixty-seven subjects from the city of Botucatu were surveyed for colonization in two other occasions, and had swabs collected from household members. The prevalence rates for S. aureus and MRSA in the first survey were 25.8% and 2.7%. The overall S. aureus colonization was negatively associated with the use of beta-lactams and of illicit drugs. On the other hand, MRSA colonized subjects were more likely to use crack and to have been admitted to a hospital during the past year. Repeated surveys found additional cases of MRSA colonization, but all subjects were positive in only one occasion. Four PFGE clusters were characterized, grouping subjects in household, city and region level. Of 19 total MRSA isolates, only one did not harbor SCCmec type IV. Spatial analysis of households of subjects living in the city of Botucatu found significant overdispersion of cases, but no association with socio-economic indicators. Conclusion: We found small but relevant prevalence of MRSA among PLWHA. Community and healthcare-associated risk factors were identified, so that predominant routes of transmission could not be determined on epidemiological grounds.