Nasal colonization with methicillin-resistant Staphylococcus aureus (MRSA) is believed to precede disease. It is therefore reasonable to expect that testing for nasal MRSA colonization could provide guidance in the choice of empirical therapy for infections. We conducted a retrospective review of 5,779 nasal MRSA tests performed within a 24-h period before or after a clinical culture showed the growth of any organism. A positive nasal MRSA test strongly predicted MRSA involvement at a clinical site (relative risk, 12.9 times higher than in the remainder of the population; 95% confidence intervals [CI], 10.4, 16.1). Nasal MRSA colonization also strongly predicted antimicrobial resistance in other organisms. A negative nasal test was less useful; only 217 of 323 patients (67.2%; 95% CI, 61.8, 72.3) with clinical cultures involving MRSA had detectable, concomitant nasal MRSA colonization. Patients with clindamycin-susceptible MRSA infections were less likely (59%) to have nasal colonization than those with clindamycin-resistant MRSA infections (71%; P = 0.042). Patients nasally colonized with MRSA were substantially more likely to have antibiotic-resistant floras in clinical specimens, and this should be considered when initiating therapy. However, nearly a third of MRSA-infected patients were not nasally colonized, suggesting that nasal colonization need not precede disease and that a negative test for nasal colonization would not rule out MRSA disease in settings of moderate or high prevalence.