Objectives: The purpose of this study is to compare the antimicrobial activity of linezolid and tigecycline with other commonly used antibiotics against a variety of clinical isolates at Royal Hospital, Muscat. Methods: Clinically-significant bacterial isolates in Royal hospital during the period from 1st of March to 30th of June 2007 were collected, stored and finally tested to determine their susceptibility to different antibiotics by broth microdilution (microscan panels). Results: Two hundred ten bacterial strains were collected and tested including Staphylococcus aureus (29), Group B ß-haemolytic Streptococcus (10), Streptococcus pneumoniae (15), Enterococcus spp. (16), Haemophilus spp. (15), Escherichia coli (26), Klebsiella spp. (26), Enterobacter spp. (25), Serratia spp. (10), Acinetobacter baumannii (17) and Pseudomonas aeruginosa (21). All strains except P. aeuginosa were susceptible to tigecycline. All grampositive strains were susceptible to linezolid. Meropenem and piperacillin-tazobactam showed good activity against most organisms tested including P. aeruginosa and Acinetobacter baumannii. Levofloxacin showed 100% activity against K. pneumoniae and 61% activity against E. coli. The activity of 3rd generation cephalosporins against E.coli and K. pneumoniae ranged from 76% to 100%. Conclusion: Tigecycline and linezolid showed excellent activity against microorganisms in their relevant spectrum of activity. However, they should be used wisely and judiciously.