Background: Soft tissue infections are one of the most common presenting problems in hospital settings. Microorganisms are commonly found in the hospital environment and are responsible for significant morbidity and mortality. Antibiotic resistance and its rapid spread in bacterial isolates are one of the biggest threats to global health. We have conducted a study to determine the bacterial etiology and its antibiotic susceptibility pattern of skin and soft tissue infection in a tertiary care hospital. Aim: To find the prevalence, bacterial profile and antimicrobial resistance pattern of skin and soft tissue infection. Results: A total of 1005 pus samples from patient were collected and cultured. Of them 28.05% positivity rate for the pathogenic bacterial isolate was observed. The most common pathogen was Klebsiellaspp (23.04%) followed by Pseudomonas aeruginosa (19.14%), Staphylococcus aureus (15.95%) and Escherichia coli (15.95%). Gram positive bacteria showed high resistance to Penicillin-G, Ampicillin, Gentamycin and Cotrimoxazole while Gram negative bacteria were more resistant to Ampicillin, Cefotaxime, Ceftazidime and Cefepime. Conclusion:Timely identification of the pathogen and its antibiogram from clinical specimen of soft tissue infection is an important function of clinical microbiology laboratory; it is beneficial for the patient in selection of appropriate antimicrobial therapy.