BACKGROUND: The 6-minute walk test distance (6MWD) predicts mortality in COPD. Whether variability in study type (observational versus interventional), region performed limits use of the test as a stratification tool or outcome measure for therapeutic trials is unclear. METHODS: Original data from 14,497 COPD patients from 6 observational (n = 9641) and 5 interventional (n=4856) studies larger than 100 patients and longer than 6 months in duration were included. The geographical, anthropometrics, FEV1, dyspnea, co-morbidities and health status scores were measured. Associations between 6MWD with mortality, hospitalizations and exacerbations adjusted by study type, age and gender were evaluated. Thresholds for outcome prediction were calculated using receiver-operating curves. The change in 6MWD after inhaled bronchodilator treatment and surgical lung volume reduction (LVRS) were analyzed to evaluate the responsiveness of the test as an outcome measure. RESULTS: The 6MWD was significantly lower in non-survivors, those hospitalized or who exacerbated compared with those without events at 6, 12 and > 12 months. At these time points, the 6MWD ROC-AUC to predict mortality was 0.71, 0.70 and 0.68 and for hospitalizations was 0.61, 0.60 and 0.59. After treatment, the 6MWD was not different between placebo or bronchodilators but increased after LVRS compared with medical therapy. Variation across study types (observational or therapeutic) or regions did not confound the ability of 6MWD to predict outcome. CONCLUSIONS: The 6MWD may help stratify COPD patients for clinical trials and interventions aimed at modifying exacerbations, hospitalizations or death.