Study objective: Pneumococcal vaccination (PV) rates for eligible emergency department patients are less than 25%. This study determines the potential effect of an ED-based pneumococcal vaccination program in preventing pneumococcal bacteremia (PB) in high-risk patients. Methods: In a retrospective observational study, hospital records of 188 consecutive adults (greater than or equal to 18 years old) with PB were reviewed to determine how many were treated in the ED from 1 to 72 months before their admission for bacteremia. Potential cost savings and mortality reductions from an ED-based PV program were calculated assuming PV prevents 65% of bacteremic episodes. A retrospective review of 10,650 ED charts determined the percentage of patients with PV indications and the relative frequency of indications. Results: One hundred four (55%) of the 188 patients with PB were seen in the ED less than or equal to 72 months before their admission for PB, and 91 (88%) of the 104 had indications for PV. These 91 patients had been evaluated in the ED an aver age of 3.4 times per patient during this 72-month period. Nine patients (10%) died before discharge. Mean hospital stay for the 82 survivors was 11.2 days. Of 10,650 ED charts reviewed, 2,011 (19%) had documented PV indications. Most prevalent PV indications were age 65 years or older (851 patients, 42%), diabetes mellitus (697, 35%), malignancy (248, 12%), chronic renal failure (228, 11%), and immunosuppression (221, 11%). Estimated cost savings ranged from $168,940 to $427,380. Conclusion: ED-based PV programs would result in considerable cost savings and decreased mortality.