To assess the economic impact of Lyme disease (LD), the most common vectorborne inflammatory disease in the United States, cost data were collected in 5 counties of the Maryland Eastern Shore from 1997 to 2000. Patients were divided into 5 diagnosis groups, clinically defined early-stage LD, clinically defined late-stage LD, suspected LD, tick bite, and other related complaints. From 1997 to 2000, the mean per patient direct medical cost of early-stage LD decreased from $1,609 to $464 (p<0.05), and the mean per patient direct medical cost of late-stage LD decreased from $4,240 to $1,380 (p<0.05). The expected median of all costs (direct medical cost, indirect medical cost, nonmedical cost, and productivity loss), aggregated across all diagnosis groups of patients, was approximately $281 per patient. These findings will help assess the economics of current and future prevention and control efforts.