Exacerbations of chronic obstructive pulmonary disease (COPD) impair health-related quality of life (HRQoL). It is unknown whether exacerbations requiring hospitalisation have an impact on HRQoL. 611 ambulatory COPD patients were prospectively identified. The average age (SD) was 65.5 (8.6), FEV(1) (SD) was 52% (14%) of the predicted value. All patients completed the Saint George's Respiratory Questionnaire (SGRQ) and the Medical Outcomes Study Short Form (SF-36) questionnaire at the beginning of the study. After five years of follow-up, the 391 survivors again completed these HRQoL instruments. No changes in HRQoL were observed among patients not hospitalised for COPD exacerbations. Those hospitalised during follow-up experienced significant declines in HRQoL. The largest changes were observed among patients with >or=3 hospitalisations, with a 13.6 unit increase in the total SGRQ and a 10.5 unit decrease in the physical component summary scale of the SF-36. Similar changes were observed among patients with FEV(1)>or=50% at baseline. In the multivariate analysis, after adjustment by FEV(1%), age, comorbidities, and HRQoL in the respective HRQoL domain at baseline, hospitalisations were an independent predictor of the change in HRQoL. Hospitalisations for exacerbations of COPD have an independent and negative impact on the evolution of HRQoL, regardless of COPD severity.