The increasing resistance to macrolide, lincosamide, streptogramin B (MLSB) agents among Staphylococcus aureus is becoming a challenge to microbiologist. Clindamycin has been a useful drug for treatment of infection caused by the staphylococcus aureus, but change in clindamycin sensitivity pattern due to various mechanisms is leading to therapeutic failure. One of the important mechanisms is mediation of resistance by erm genes. Staphylococcus strains which have erm genes show inducible clindamycin resistance that cannot be determined by routine disk diffusion test resulting in treatment failure. Resistance may be constitutive (cMLSB phenotype) or inducible (iMLSB phenotype).The iMLSB phenotypes are distinguished by erythromycin-clindamycin disk approximation test. A total of 142 clinically significant Staphylococcus aureus isolated from pus, urine, blood, fluid, sputum, ear swabs, endotrachealtube, ophthalmic , and umbilical discharge.These isolates were initially identified by colony morphology, Gram staining, catalase test, slide coagulase test, tube coagulase test and mannitol fermentation. The isolates were subjected to routine antibiotic sensitivity testing including cefoxitin by Kirby Bauer disk diffusion test.Inducible clindamycin resistance was detected by double disk approximation test (D-test)as per CLSI guidelines on erythromycin resistant isolates.For detection of inducible clindamycin resistance, D test using erythromycin and clindamycin as per CLSI guidelines was performed, and three different phenotypes were interpreted as methicillin-sensitive (MS) phenotype (D test negative), inducible MLSB (iMLSB) phenotype (D test positive), and constitutive MLSB phenotype. Of the 142 isolates, 50 were identified as methicillin resistant S. aureus, while 92 were methicillin sensitive S. aureus. The rates of inducible clindamycin resistance in methicillin resistant S. aureus (MRSA), methicillin sensitiveS. aureus (MSSA) were 36% and 2.2%, respectively. The inducible clindamycin resistance was significantly more among MRSA compared to methicillin sensitive S. aureus (MSSA) (P value < 0.0001). Overall the rate of inducible clindamycin resistance is 14.1%,constitutive clindamycin resistance 2.8% and MS phenotype is 6.3%. Majority of the MRSA isolates were susceptible to clindamycin, vancomycin and linezolid, while most of them were resistant to erythromycin,gentamicin,ciprofloxacin,tetracycline and sulfamethoxazole-trimethoprim. Clindamycin is the drug of choice in many staphylococcal,streptococcal and anaerobic infections.The D-test is easy to perform and inexpensive to know clindamycin sensitivity. We feel that this test should be made mandatory as a routine work in clinical microbiology laboratories. Therapeutic failures can be prevented if we don t use clindamycin for treatment of patients with infections caused by staphylococci with inducible clindamycin resistance.