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Pneumococcal conjugate vaccine for infants has recently been found to be effective for prevention of meningitis, bacteremia, pneumonia and otitis media, but it is more costly than previously introduced vaccines.We sought to determine the savings in medical costs through 36 months of life attributable to the use of the vaccine in healthy infants in a large randomized trial.We analyzed the actual medical costs of 36 471 children involved in a randomized trial of heptavalent pneumococcal conjugate vaccine conducted in the Northern California Kaiser Permanente Medical Care Program. The costs of the vaccine and vaccine administration were excluded.Compared with the control group, the vaccinated group experienced a 2% reduction in clinic related costs [$48; 95% confidence interval (CI), $10 to $83] and a nearly significant 14% reduction in outpatient hospitalization costs ($32; CI −$1 to $66). The savings in total medical costs were 1.2%, but this difference was not significant ($41; CI −$204 to $270). Inpatient hospital costs were highly variable and were responsible for the lack of precision in the difference in total cost. In a post hoc analysis that excluded hospital costs not believed to be potentially pneumococcal related, savings in medical costs were $78 and significant (CI $5 to $158).The pneumococcal conjugate vaccine reduced ambulatory care costs in children in the first 36 months of life, but without a larger trial, the magnitude of the savings in total medical costs is uncertain. These results indicate, however, that any medical cost savings that are associated with the vaccine are unlikely to be high enough to offset the cost of the vaccine at its current price.