Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality in the United States. In 2000, an estimated 10.5 million people had COPD, of which more than 7.2 million were from the under-age 65 employed population. The prevalence of COPD in the workforce population was substantial with 46.5% of current employment among adults having the disease. However, the cost burden in the employed population is unknown. We examined COPD prevalence and costs in a large employment-based population. Using claims data from 1999 to 2003, we estimated the cost associated with COPD-related hospitalizations, emergency department visits, outpatient services, and prescription drug use. Per patient use of hospital care for COPD decreased during 1999 through 2003, including a decrease in the number of hospital admissions (from 0.10 in 1999 to 0.04 in 2003) and in the length of stay in hospitals (from 0.53 in 1999 to 0.17 in 2003). The number of outpatient visits, however, increased from 3.45 in 1999 to 3.80 in 2003. COPD-related per patient total medical costs decreased from $1460 in 1999 to $1138 in 2003 largely because of a decrease in the cost of hospitalizations for COPD. In contrast, mean per patient expenditures for outpatient services increased over the same period from $243 in 1999 to $295 in 2003. The cost of COPD to employers is high, but the cost could be reduced by programs aimed at preventing new cases of COPD, reducing hospitalizations, and providing more outpatient services to COPD patients.