The aim of this study was to evaluate whether changes in regular physical activity (PA) affect health-related quality of life (HRQoL) among patients with chronic obstructive pulmonary disease (COPD). 611 patients (mean age 67.2+/-8.4 yrs; forced expiratory volume in 1 s 49.7+/-14.6) completed the St George's Respiratory Questionnaire (SGRQ), the Chronic Respiratory Questionnaire (CRQ) and the Medical Outcomes Short Form (SF-36) questionnaire. PA, defined as patients' self-reported regular walking times, was classified as low, moderate and high. After 5 yrs, 391 survivors completed these instruments again. After adjustment for relevant confounders, patients who reported low PA at baseline and who increased their PA over the study period improved their SGRQ and CRQ scores by 15.9 and 8.7 points, respectively. Patients who moved from moderate to high PA improved their SGRQ scores by 18.4 and their CRQ scores by 14.8. Slightly smaller increases were observed for patients who maintained a high level of PA throughout the study period. Maintaining a low level of PA or decreasing PA over the study period was associated with a significant HRQoL decline. Among COPD patients, a reduction in time spent engaging in PA or maintaining a low level may impair HRQoL, whereas an increase in PA can improve HRQoL parameters.