BACKGROUND: Following the introduction of a 7-valent pneumococcal conjugate vaccine for children in 2000, there has been a decrease in the incidence of invasive pneumococcal disease among both children and adults in the United States. We evaluated the hypothesis that the case-fatality and mortality rates for invasive pneumococcal disease have also decreased since 2000. METHODS: We conducted a population-based outcome study in Olmsted County, Minnesota, during the period 1995-2007 that involved patients of all ages. RESULTS: From 1 January 1995 through 31 December 2007, a total of 180 eligible cases of invasive pneumococcal disease were identified in Olmsted County. During the 13-year study period, the overall case-fatality rate for invasive pneumococcal disease decreased from 19% (14 of 74 cases) in 1995-1999 to 5% (5 of 91 cases) in 2001-2007, an 83% decrease, after adjustment for age, sex, and Charlson comorbidity index score (P =.003). The largest decreases in case-fatality rate were seen among adults aged >/=65 years (an 86% decrease, from 31% [9 of 29 cases] to 8% [3 of 40 cases]; P=.02) and patients with invasive pneumonia (a 78% decrease, from 22% [12 of 55 cases] to 7% [5 of 72 cases]; P=.01). The overall mortality rate for invasive pneumococcal disease decreased from 2.9 deaths per 100,000 person-years in 1995-1999 to 0.7 deaths per 100,000 person-years in 2001-2007, a 78% decrease, after adjustment for age and sex in a Poisson regression model (P=.002). CONCLUSIONS: Significant decreases in the case-fatality and mortality rates for invasive pneumococcal disease were demonstrated in the population of Olmsted County. Additional studies are needed to confirm our findings in other populations.