Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality in industrialized countries. Recent studies investigated the impact of comorbidities on the survival in COPD, but most of them lacked a referent group of comorbidity-matched, nonobstructed individuals.We examined the 10-year mortality in a sample of 200 COPD patients and 201 nonobstructed controls. They were part of a larger cohort enrolled in a European case-control study aimed at assessing genetic susceptibility to COPD. By design, the COPD group included patients with a forced expiratory volume in 1 second (FEV1) ≤70% predicted. Cases and controls were matched on age, sex, and cumulative smoking history, and shared a nearly identical prevalence of cardiovascular and metabolic disorders. We estimated the hazard of death with Cox regression and percentiles of survival with Laplace regression. COPD was the main exposure variable of interest. Five comorbidities (hypertension, coronary artery disease, prior myocardial infarction, chronic heart failure, and diabetes) were included as covariates in multiple regression models.The all-cause mortality rate was significantly higher in cases than in controls (43% vs 16%, P < 0.001). The unadjusted hazard of death for COPD was 3-fold higher than the referent category (P < 0.001), and remained nearly unchanged after introducing the 5 comorbidities in multiple regression. Patients with COPD had significantly shorter survival percentiles than comorbidity-matched controls (P < 0.001). Notably, 15% of the nonobstructed controls died by 10.3 years into the study; the same proportion of COPD patients had died some 6 years earlier, at 4.6 years.In a separate analysis, we split the whole sample into 2 groups based on the lower tertile of FEV1 and carbon monoxide lung diffusing capacity (DLCO). The hazard of death for COPD patients with low FEV1 and DLCO was nearly 3.5-fold higher than in all the others (P < 0.001), and decreased only slightly after introducing age and chronic heart failure as relevant covariates.COPD is a strong predictor of reduced survival independently of coexisting cardiovascular and metabolic disorders. Efforts should be made to identify patients at risk and to ensure adherence to prescribed therapeutic regimens.