To identify factors associated with developing nosocomial bloodstream infection (NBI) and to identify factors associated with fatal outcome of NBI. Prospective matched and unmatched case-control studies. Songklanagarind Hospital, a 640-bed medical school and referral center in Songkla, Thailand. During a two-year study period, 277 patients of 17,829 total admissions in the hospital services of medicine, surgery, pediatrics, and orthopedics acquired bloodstream infections during hospitalization. For the purpose of identifying factors associated with mortality attributed to NBI, patients who died from NBI were assigned as cases; patients who survived the infections were assigned as controls. For the purpose of identifying risk factors for acquisition of NBI, patients with NBI were considered as cases; patients with the same primary diagnosis as a case but without NBI were eligible to be case-matched controls. Case fatality rate was 37.2% based on deaths attributed specifically to bloodstream infection. Patients who died from NBI, compared with those who survived such infections, were associated with inappropriate antibiotic treatment, infection caused by Klebsiella pneumoniae, and the medicine service. When comparison was made between 239 patients with bloodstream infections and 598 diagnosis-matched controls with no bloodstream infection, infection was found to be associated with old age, number of comorbidities, number of prior infections, neutropenia, duration of immunosuppressive drugs, and duration of indwelling intravenous catheter. Awareness of the factors pre-disposing to NBI may permit better surveillance and better care. Although most of the factors associated with development of NBI or death from NBI are not subject to control, some factors are duration of immunosuppressive drugs, duration of indwelling intravenous lines, and choice of antibiotic treatment.