To assess whether generic and specific health-related quality of life (HRQL) are independently associated with total and specific mortality in patients with chronic obstructive pulmonary disease (COPD), we followed until 1999 a cohort of 321 male patients with COPD, recruited in 1993-1994 at outpatient respiratory clinics. Baseline characteristics recorded under stable clinical conditions included forced spirometry, arterial blood gas tensions, dyspnea scales, 11 comorbid conditions, St. George's Respiratory Questionnaire (SGRQ), and SF-36 Health Survey. Vital status was assessed through reinterviews, the Mortality Register, and clinical records. Subjects who died (106) were older (69.8 versus 62.5 years) (p < 0.001), had lower body mass index (BMI) (25.4 versus 27.1) (p < 0.01), were more impaired in the clinical characteristics studied (%FEV(1), 34.0 versus 51.0) (p < 0.001), and had long-term oxygen therapy more frequently (31% versus 7%) (p < 0.001). Survival was shorter when worse HRQL was reported. SGRQ total and SF-36 physical summary scores were independently associated with total and respiratory mortality in Cox models, including age, FEV(1), and BMI. The total mortality-standardized hazard ratios for both HRQL measures were 1.3, whereas those for FEV(1) were 1.6. HRQL measures provide independent and relevant information on the health status of male patients with COPD. Their use should be considered for a more thorough evaluation and staging of patients with COPD.