Objective: Chronic lung disease has been associated with greater impairment in self-reported physical function in HIV-infected patients. We sought to study this association using objective measures of physical function and pulmonary function. Design: Baseline data from the Examinations of HIV Associated Lung Emphysema study, a multicenter observational cohort of HIVinfected and uninfected veterans. Methods: We assessed the association between clinical, laboratory, and pulmonary function measures with 6-minute walk test (6-MWT). Multivariable linear regression models were generated to identify factors associated with 6-MWT performance. Results: Three hundred forty participants completed 6-MWT (mean age 55 years), with 68% blacks, 94% men, and 62% current smokers. Overall, 180 (53%) were HIV-infected and 63 (19%) had spirometry-defined chronic obstructive pulmonary disease. In a multivariable model, age, current smoking, and obesity (body mass index < 30) were independently associated with lower 6-MWT performance, but HIV infection was not; there was a significant interaction between HIV and chronic cough, such that distance walked among HIV-infected participants with chronic cough was 51.76 m less (P = 0.04) compared with those without cough or HIV. Among HIV-infected participants, the forced expiratory volume in 1 second (FEV1, percent predicted), to a greater extent than total lung capacity or diffusing capacity, attenuated the association with chronic cough; decreased FEV1 was independently associated with lower 6-MWT performance in those with HIV. Conclusions: Older age, current smoking, and airflow limitation were important determinants of 6-MWT performance in the HIVinfected participants. These findings suggest that potential interventions to improve physical function may include early management of respiratory symptoms and airflow limitation.