The Emergency Department is a suitable but challenging environment to implement a sustainable pneumococcal vaccination program. To increase vaccination rates for patients > or equal to 65 years old, we prospectively evaluated a closed-loop informatics approach over a 6-week study period. Among the 572 candidate patients, 284 were up-to-date with vaccination, 187 patients refused vaccination, 65 physicians declined to order the vaccine, and 28 patients received the vaccine during the ED visit. The informatics approach increased vaccination rate from a baseline of 49.8% to 54.9% (p < 0.01).