A major concern while prescribing clindamycin to treat infections caused by inducible macrolide, lincosamide, and group B streptogramin (iMLS(B))-resistant strains is clinical therapy failure. In this study, we determined the prevalence, mechanism, and clonality of the iMLS(B) phenotype in oxacillin-resistant Staphylococcus aureus (ORSA) and oxacillin-susceptible S. aureus (OSSA). Among the 729 OSSA isolates collected from July 1995 to March 2006, 72 (10%) were clindamycin sensitive (Cli(s)) and erythromycin resistant (Erm(r)), and 55 (8%) had the iMLS(B) phenotype. In the 709 ORSA isolates collected from January 1997 to March 2006, 31 (4%) were Cli(s) and Erm(r), and 29 (4%) isolates demonstrated the iMLS(B) phenotype. In OSSA, ermC was the predominant (51 of 55 isolates) genetic determinant responsible for the iMLS(B) phenotype, whereas in ORSA, ermA was predominant (27 of 29). Pulsed-field gel electrophoresis showed that 8 pulsed types (RA to RH) were present in ORSA isolates (n = 27), and pulsed type RC was predominant in 17 isolates with 5 identifiable subtypes (RC1 to RC5); this type was prevalent from November 1997 to June 2004. In the OSSA (n = 24) isolates, 14 different pulsed types (SA to SN) were identified, but none was predominant. These results indicate that the incidence of iMLS(B) resistance phenotype is higher in OSSA than ORSA in Taiwan, and the genetic determinants responsible for the iMLS(B) phenotype vary in OSSA and ORSA.