To determine the cost effectiveness of vaccinating against Lyme disease, we used a decision tree to examine the impact on society of six key components. The main measure of outcome was the cost per case averted. Assuming a 0.80 probability of diagnosing and treating early Lyme disease, a 0.005 probability of contracting Lyme disease, and a vaccination cost of $50 per year, the mean cost of vaccination per case averted was $4,466. When we increased the probability of contracting Lyme disease to 0.03 and the cost of vaccination to $100 per year, the mean net savings per case averted was $3,377. Since few communities have average annual incidences of Lyme disease >0. 005, economic benefits will be greatest when vaccination is used on the basis of individual risk, specifically, in persons whose probability of contracting Lyme disease is >0.01.