The effectiveness of pneumococcal vaccine in the immunocompetent elderly remains controversial. We report the results of a multicenter, case-control study of 244 controls and 122 patients, aged 55 years and older, hospitalized during a 5-year period with pneumococcal bacteremia, meningitis, or other bacteriologically confirmed pneumococcal infection. Two controls per patient were matched on the basis of admission date, hospital records, and underlying diseases. All subjects were selected without knowledge of immunization status with pneumococcal vaccine, and were excluded if there was evidence for immunosuppression due to disease or iatrogenic causes. The clinical effectiveness of the vaccine was calculated to be 70% (95% confidence intervals [CI], 37% to 86%) in this population, based on a Mantel-Haenszel point estimate of the odds ratio of 0.30 (95% CI, 0.14% to 0.63%; P less than 0.005). The clinical effectiveness of pneumococcal vaccine in preventing pneumococcal infection in the immunocompetent elderly approximates the vaccine's effectiveness in the general immunocompetent population.