Purpose: Limited evidence in the United States suggests that among patients with chronic obstructive pulmonary disease (COPD), rural residence is associated with higher hospitalization rates and increased mortality. However, little is known about the reasons for these disparities. This study's purpose was to describe the health status of rural versus urban residence among patients with COPD and to examine factors associated with differences between these 2 locations. Methods: This was a cross-sectional study of baseline data from a representative sample of patients with COPD enrolled in a clinical trial. Rural-urban residence was determined from ZIP code. Health status was measured using the SF-12 and health care utilization. Independent sample t-tests, chi-square tests, and multiple linear and logistic regressions were performed to examine differences between rural and urban patients. Findings: Rural residence was associated with poorer health status and higher health care utilization. Among rural patients unadjusted physical functioning scores were lower on the SF-12 (30.22 vs 33.49; P = .005) that persisted after adjustment for potential confounders (β = -2.35; P = .04). However, after further adjustment for social and psychological factors only the body-mass index, airflow obstruction, dyspnea, and exercise (BODE) index was significantly associated with health status. Conclusions: In this representative sample of patients with COPD rural residence was associated with worse health status, primarily associated with greater impairment as measured by BODE index. While rural patients reported a higher dose of smoking, a number of other unmeasured factors associated with rural residence may contribute to these disparities. © 2013 National Rural Health Association.