To define the influence of prognostic factors in patients with community-acquired pneumococcal bacteremia, a 2-year prospective study was performed in 5 centers in Canada, the United States, the United Kingdom, Spain, and Sweden. By multivariate analysis, the independent predictors of death among the 460 patients were age >65 years (odds ratio [OR], 2.2), living in a nursing home (OR, 2.8), presence of chronic pulmonary disease (OR, 2.5), high acute physiology score (OR for scores 9-14, 7.6; for scores 15-17, 22; and for scores >17, 41), and need for mechanical ventilation (OR, 4.4). Of patients with meningitis, 26% died. Of patients with pneumonia without meningitis, 19% of those with >/=2 lobes and 7% of those with only 1 lobe involved (P=.0016) died. The case-fatality rate differed significantly among the centers: 20% in the United States and Spain, 13% in the United Kingdom, 8% in Sweden, and 6% in Canada. Differences of disease severity and of frequencies and impact of underlying chronic conditions were factors of probable importance for different outcomes.