BACKGROUND: Salmonella enterica is an important emerging cause of invasive infections worldwide. However, population-based data are limited. The objective of this study was to define the occurrence of S. enterica bacteremia in a large international population and to evaluate temporal and regional differences. METHODS: We conducted population-based laboratory surveillance for all salmonella bacteremias in six regions (annual population at risk 7.7 million residents) in Finland, Australia, Denmark, and Canada during 2000-2007. RESULTS: A total of 622 cases were identified for an annual incidence of 1.02 per 100,000 population. The incidence of typhoidal (serotypes Typhi and Paratyphi) and non-typhoidal (other serotypes) disease was 0.21 and 0.81 per 100,000/year. There was major regional and moderate seasonal and year to year variability with an increased incidence observed in the latter years of the study related principally to increasing rates of non-typhoidal salmonella bacteremias. Advancing age and male gender were significant risk factors for acquiring non-typhoidal salmonella bacteremia. In contrast, typhoidal salmonella bacteremia showed a decreasing incidence with advancing age and no gender-related excess risk. CONCLUSIONS: Salmonella enterica is an important emerging pathogen and regional determinants of risk merits further investigation.