OBJECTIVE: To establish the minimal important difference (MID) for the six-minute walk distance (6MWD) in persons with chronic obstructive pulmonary disease (COPD). DESIGN: Analysis of data from an observational study using distribution- and anchor-based methods to determine the MID in 6MWD. SETTING: Outpatient pulmonary rehabilitation program at 2 teaching hospitals. PARTICIPANTS: Seventy-five patients with COPD (44 men) in a stable clinical state with mean age 70 years (SD 9 y), forced expiratory volume in one second 52% (SD 21%) predicted and baseline walking distance 359 meters (SD 104 m). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Participants completed the six-minute walk test before and after a 7-week pulmonary rehabilitation program. Participants and clinicians completed a global rating of change score while blinded to the change in 6MWD. RESULTS: The mean change in 6MWD in participants who reported themselves to be unchanged was 17.7 meters, compared with 60.2 meters in those who reported small change and 78.4 meters in those who reported substantial change (P=.004). Anchor-based methods identified an MID of 25 meters (95% confidence interval 20-61 m). There was excellent agreement with distribution-based methods (25.5-26.5m, kappa=.95). A change in 6MWD of 14% compared with baseline also represented a clinically important effect; this threshold was less sensitive than for absolute change (sensitivity .70 vs .85). CONCLUSIONS: The MID for 6MWD in COPD is 25 meters. Absolute change in 6MWD is a more sensitive indicator than percentage change from baseline. These data support the use of 6MWD as a patient-important outcome in research and clinical practice.