To better understand the epidemiology of bacterial pathogens with particular public health importance in Taiwan, we determined the prevalence of nasal colonization with methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) in a cohort of HIV-infected patients attending two hospital outpatient departments. All HIV-infected patients followed regularly between May and September 1999 were enrolled and cultures of the anterior nares were performed using a dry sponge swab. All confirmed S. aureus isolates underwent antimicrobial susceptibility testing using disk diffusion according to recommendations of the National Committee for Clinical Laboratory Standards. Of a total of 162 outpatients studied, 48 (30%) were found colonized with S. aureus including 39 (24%) colonized with MSSA and 9 (6%) colonized with MRSA. The only factor associated with MSSA colonization was receipt of trimethoprim-sulphamethoxazole which appeared protective (relative risk 0.4, 95% confidence interval [CI(95)] 0.2-0.78, P = 0.006). In contrast, ciprofloxacin use was an independent risk factor for MRSA colonization (conditional odds ratio [OR] 11.9, CI(95) 1.8-77.8, P = 0.010) along with a one-quartile reduction in CD(4) count (OR 3.9, CI(95) 1.1-14.3, P = 0.04). Although MRSA colonization was not associated with hospitalization within the previous three months, the multi-drug resistance pattern of MRSA isolates suggests strains were at some point acquired in the healthcare setting. Our study shows that the rate of S. aureus colonization in Taiwanese HIV-infected outpatients is 30%. Low CD4+ counts are most likely associated with other unmeasured risk factors for MRSA. Antimicrobial use may function alternatively as a protective or risk factor for colonization with S. aureus, depending upon the drugs involved and resistance encountered. Fluoroquinolone use may have an important role in the spread of MRSA from inpatient to outpatient settings.