This study investigated the prevalence of resistance to macrolides, lincosamides, and streptogramin B (MLSB) in Staphylococcus aureus isolates from a tertiary care hospital in India. The study detected the erm A and erm C genes in isolates that showed inducible clindamycin resistance (MLSB i). The overall prevalence of MLSB i resistance was found to be 10.8% and the prevalence of constitutive resistance (MLSB c) was 11.6%. The erm A and erm C genes were detected in MLSB i isolates, demonstrating that methylation of the 23S rRNA is a mechanism of MLSB resistance in these clinical S. aureus strains.