Background Blood stream infections (BSIs) are important determinants for prolonged hospital stay and if uncontrolled, progress to become life-threatening. The aim of this study is to determine the common bacterial agents associated with BSI and their antimicrobial susceptibility patterns in a tertiary care teaching hospital in the Western region of Nepal. Method A cross-sectional study was conducted for a 20 month period from January 2006 to August 2007. All adult patients with fever (temperature ≥ 38°C) when assessed in the outpatient department or various inpatient wards were enrolled in the study. Results Of the 933 patients with febrile illness, only 96 were diagnosed to have BSIs. Salmonella spp., Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus were the common etiological agents of BSIs. S. Paratyphi A and S. Paratyphi B were responsible for 46.7% of the enteric fever cases. The clinical diagnosis of enteric fever was not sensitive and specific. The members of Enterobacteriaceae were frequently resistant to ampicillin, amoxicillin/ clavulanic acid and gentamicin. About one-third of the K.pneumoniae, E.coli and Enterobacter spp. produced extended-spectrum β-lactamases. The non-fermenters were unusually sensitive to most antibiotics. Conclusion Gram-negative bacteria were the predominant causes of BSIs. The occurrence of drug resistant S. Paratyphi A is of great concern for travellers, as they are not protected with an effective vaccine. Imipenem showed good activity against Pseudomonas aeruginosa indicating lack or low level of MBL activity