BACKGROUND: The epidemiology of staphylococcal colonization and community-associated methicillin-resistant Staphylococcus aureus (MRSA) is changing, and little is known from the national perspective. OBJECTIVE: To describe the U.S. epidemiology of S. aureus nasal colonization, compare risk factors for colonization with methicillin-sensitive S. aureus (MSSA) versus MRSA, and compare antibiotic resistance patterns and genetic factors of colonizing strains of S. aureus. DESIGN: Secondary analysis of data from the National Health and Nutrition Examination Survey (NHANES), a stratified, multistage probability sample. SETTING: United States. PARTICIPANTS: 2001-2002 NHANES participants older than 1 year of age. MEASUREMENTS: Colonization of MSSA and MRSA, risk factors for colonization, antimicrobial resistance, and percentage of isolates with selected genetic factors. RESULTS: The prevalence of colonization with S. aureus and with MRSA was 31.6% and 0.84%, respectively, in the noninstitutionalized U.S. population. People younger than 65 years of age, men, persons with less education, and persons with asthma were more likely to acquire S. aureus. Persons of black race and those of Mexican birth had lower risk for S. aureus colonization. Persons 65 years of age or older, women, persons with diabetes, and those who were in long-term care in the past year were more likely to have MRSA colonization. Hispanic persons had statistically significantly less risk than white persons. Isolates of MRSA with staphylococcal chromosomal cassette mec type IV (which is often associated with community-associated MRSA) were statistically significantly more likely to be sensitive to erythromycin, clindamycin, and ciprofloxacin. LIMITATIONS: Colonizing isolates may be different from isolates associated with infection. Risk factors identified may differ from those associated with invasive disease. The 2001-2002 NHANES data are several years old and may not reflect the most recent changes in epidemiology, but they are the only national data available. CONCLUSIONS: Characteristics of persons with MSSA and MRSA seem to differ. These findings may be useful for differentiating those who may be at risk for MRSA.