BACKGROUND Estimates of the prevalence of colonization with methicillin-resistant Staphylococcus aureus (MRSA) vary in HIV-infected patients. METHODS HIV clinic patients were prospectively cultured. Bilateral nasal and axillary swabs were plated on BBL CHROMagar MRSA media. Molecular typing was done by pulse-field gel electrophoresis, and staphylococcal cassette chromosomemec typing was determined. A patient questionnaire was conducted to ascertain potential MRSA risk factors; medical records were reviewed. RESULTS Fifteen of 146 (10.3%) patients had MRSA nasal colonization; 1 also had axillary colonization. Twelve of 15 isolates were staphylococcal cassette chromosomemec type IV, and 8 of 14 were USA300 or USA400 genotype. MRSA colonization was associated with lower CD4 cell count, not receiving current or recent antibiotics, history of prior MRSA or methicillin-susceptible Staphylococcus aureus infection (P < 0.05 for all), and a trend toward history of hospitalization or emergency department visit in the past year (P = 0.064). Current use of trimethoprim-sulfamethoxazole was protective for colonization: 0 of 29 trimethoprim-sulfamethoxazole recipients were colonized versus 15 of 117 nonrecipients, P = 0.04. In a multivariate logistic regression model, prior infection with either methicillin-susceptible S. aureus (odds ratio = 32.4, 95% confidence interval 3.04 to 345.42) or MRSA (odds ratio = 9.71, 95% confidence interval 2.20 to 43.01), not receiving current or recent antibiotics (odds ratio = 0.026, 95% confidence interval 0.002 to 0.412), and lower CD4 count (odds ratio 0.996, 95% confidence interval 0.992 to 0.999) were associated with MRSA colonization. DISCUSSION The prevalence of MRSA nasal colonization was relatively high compared with prior studies; axillary colonization was rare. Prior staphylococcal infection (methicillin-susceptible S. aureus or MRSA), not receiving antibiotics, and lower CD4 count were associated with MRSA nasal colonization. Trimethoprim-sulfamethoxazole seemed to be protective of MRSA colonization.