<b><i>Background:</i></b> Although chronic obstructive pulmonary disease (COPD) is a major cause of disability worldwide, its determinants remain poorly defined. <b><i>Objective:</i></b> We hypothesized that both pulmonary and extra-pulmonary factors would predict prospective disablement across a hierarchy of activities in persons with COPD. <b><i>Methods:</i></b> Six hundred and nine participants were studied at baseline (T₀) and 2.5 years later (T<sub>1</sub>). The Valued Life Activities (VLA) scale quantified disability (10-point scale: 0 = no difficulty and 10 = unable to perform), defining disability as any activity newly rated ‘unable to perform' at T<sub>1</sub>. Predictors included pulmonary (lung function, 6-minute walk distance and COPD severity score) and extra-pulmonary (quadriceps strength and lower extremity function) factors. Prospective disability risk was tested by separate logistic regression models for each predictor (baseline value and its change, T₀-T<sub>1</sub>; odds ratios were scaled at 1 standard deviation per factor. Incident disability across a hierarchy of obligatory, committed and discretionary VLA subscales was compared. <b><i>Results:</i></b> Subjects manifested a 40% or greater increased odds of developing disability for each predictor (baseline and change over time). Disability in discretionary activities developed at a rate 2.2-times higher than observed in committed activities, which was in turn 2.5-times higher than the rate observed in obligatory activities (p < 0.05 for each level). <b><i>Conclusions:</i></b> Disability is common in COPD. Both pulmonary and extra-pulmonary factors are important in predicting its development.