Although community-onset bloodstream infection (BSI) is recognized to be a major cause of morbidity and mortality, there is a paucity of population-based studies defining its overall burden. We conducted population-based laboratory surveillance for all community-onset BSI in the Calgary Health Region during 2000-2004. A total of 4467 episodes of community-onset BSI were identified for an overall annual incidence of 81.6/100,000. The three species, Escherichia coli, Staphylococcus aureus, and Streptococcus pneumoniae were responsible for the majority of community-onset BSI; they occurred at annual rates of 25.8, 13.5, and 10.1/100,000, respectively. Overall 3445/4467 (77%) episodes resulted in hospital admission representing 0.7% of all admissions to major acute care hospitals. The subsequent hospital length of stay was a median of 9 (interquartile range, 5-15) days; the total days of acute hospitalization attributable to community-onset BSI was 51,146 days or 934 days/100,000 annually. Four hundred and sixty patients died in hospital for a case-fatality rate of 13%. Community-onset BSI is common and has a major patient and societal impact. These data support further efforts to reduce the burden of community-onset BSI.