Methicillin-resistant Staphylococcus aureus (MRSA) infections have become common among both hospitalized and nonhospitalized patients. Optimal outpatient therapy for MRSA infections has yet to be determined, but this matter is complicated by the possibility of inducible macrolide-lincosamide-streptogramin B resistance (MLSBi). We studied the prevalence of MLSBi in community- and hospital-associated S. aureus isolates and the prevalence of community-associated MRSA (CA-MRSA) and identified clinical predictors of CA-MRSA and MLSBi. Among 402 S. aureus isolates, the overall prevalence of MLSBi was 52%, with 50% of MRSA and 60% of methicillin-susceptible S. aureus isolates exhibiting MLSBi. CA-MRSA represented 14% of all isolates and had a lower prevalence of MLSBi than hospital-associated MRSA (33% versus 55%). The presence of skin or soft-tissue infection was predictive for CA-MRSA, and the presence of a comorbidity was predictive for MLSBi. Due to the low prevalence of MLSBi among CA-MRSA isolates, clindamycin remains a useful option for outpatient therapy. Copyright © 2006, American Society for Microbiology. All Rights Reserved.