COPD is one of the leading causes of mortality and morbidity in the United States, yet little is known about the prevalence of comorbid conditions and mortality in hospitalized patients with COPD. From the National Hospital Discharge Survey, 1979 to 2001, we evaluated whether or not COPD in adults > or = 25 years old is associated with increased prevalence and in-hospital mortality of several comorbidities. During 1979 to 2001, there were an estimated total of 47,404,700 hospital discharges (8.5% of all hospitalizations in adults > 25 years old) of patients with COPD; 37,540,374 discharges (79.2%) were made with COPD as a secondary diagnosis, and 9,864,278 discharges (20.8%) were made with COPD as the primary diagnosis. The prevalence and in-hospital mortality for pneumonia, congestive heart failure, ischemic heart disease, thoracic malignancies, and respiratory failure were larger in hospital discharges with any mention of COPD. In a nationally representative sample of hospitalizations, any mention of COPD in the discharge diagnosis is associated with higher hospitalization prevalence and in-hospital mortality from other comorbidities. These results highlight the fact that the burden of disease associated with COPD is likely underestimated.