Introduction:The inappropriate use of antibiotics has contributed to a worldwide problem of antimicrobial resistance. The objective of present study is to assess the most common microorganisms causing orofacial infections and their antimicrobial susceptibility to routinely used antibiotics in this part of India.Materials and Methods:Sixty eight patients with orofacial infection were selected on the basis of a series of predefined inclusion and exclusion criteria. Samples were collected under aseptic conditions and subjected to culture and antibiotic susceptibility testing. Descriptive statistics were provided.Results:A total of 64 aerobic and 87 anaerobic strains were isolated. The predominant bacteria were Streptococci viridans (64%), Prevotella (43%), Peptostreptococcus (26%), Porphyromonas (7%), and Fusobacterium (14%). The isolated strains seemed to be highly sensitive to the routinely used antibiotics such as amoxicillin – clavulanate and amoxicillin alone, clindamycin, and levofloxacin. In contrast, more resistance to erythromycin was observed.Conclusion:Amoxicillin still possesses powerful antimicrobial activity against major pathogens in orofacial odontogenic infections. Amoxicillin/clavulanate and clindamycin would also be advocated as being useful alternatives for the management of severe orofacial infections. However, the findings of this study indicate that erythromycin is of questionable benefit in the treatment of severe orofacial odontogenic infections.