BACKGROUND: Exercise tolerance is an important clinical aspect of chronic obstructive pulmonary disease that can be easily and reliably measured with the 6-minute walking test (6MWT). To improve the utility of the 6MWT for patient and health care system management, the interpretation of the functional status measure in relation to death and hospitalization should be elucidated. METHODS: Three-year, prospective, multicenter observational study to evaluate the predictive power of 6MWD for death or exacerbation-related hospitalization and to evaluate the factors that help determine 6MWD. RESULTS: We measured 6MWD at baseline and annually in 2110 patients with clinically stable Global Initiative for Obstructive Lung Disease (GOLD) stage II-IV COPD and recorded exacerbation-related hospitalizations and all-cause mortality. During the study, 200 patients died and 650 were hospitalized. Using receiver operating characteristics, the best predictive thresholds of the 6MWD were 334 m for increased risk of death and 357 m for exacerbation-related hospitalization (area under the curve 0.67 and 0.60 respectively); however, the discriminatory thresholds, especially for mortality, were influenced by age. The mean (SE) 6MWD declined by 1.6 (1.2) m per year in GOLD II, 9.8 (1.3) m per year in GOLD III, and 8.5 (2.4) m per year in GOLD IV. CONCLUSION: The 6MWD provides prognostic information that may be useful for identifying high-risk patients with COPD.