Objective: The present study was conducted to evaluate the in vitro activity of tigecycline against a contemporary collection of multidrug resistant (MDR) bacterial isolates by disc diffusion and MIC by E-Test method. Methods: A total of 100 non repetitive clinically significant MDR bacterial isolates from urine, pus, sputum endotracheal aspirates, Skin and soft tissue and surgical site infection of patients in a tertiary care teaching hospital in Karnataka, south India from March 2013 to December 2013 were included in the study. MDR bacteria tested for Tigecycline susceptibility were: Methicillin resistant S.aureus (MRSA) (15), ESBL producing Escherichia coli (E.col) (15), Klebsiella pneumoniae (35) and MDR Acinetobacter species (35). Result: Tigecycline was found to be effective against all MRSA, MDR E.coli and Acinetobacter isolates by disc diffusion and E-test method. Among the selected K. pneumoniae isolates all were sensitive by disc diffusion and 34 (97.1%) were found sensitive with the MIC range 0.25- 1.5__ampersandsignmu;g/ml, One (2.9%) isolate was found intermediate resistant with the MIC of 3__ampersandsignmu;g/ml by E-test. Conclusion: To conclude, the present study showed that, tigecycline is a potent antimicrobial agent against MRSA, ESBL producing Enterobacteriaceae Acinetobacter species and disc diffusion is simple to perform, highly reproducible and inexpensive method to predict tigecycline resistance. It is also prudent to reserve tigecycline for life threatening infections.