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Objectives: Chronic obstructive pulmonary disease (COPD) is a common comorbidity in patients with heart failure (HF). We aimed to assess its prevalence, characterization and long-term prognostic impact in the GISSI-HF population. Methods: The study randomized 6,975 ambulatory HF patients to either n-3 polyunsaturated fatty acids or placebo. We performed a retrospective analysis of clinical characteristics and outcomes of the 1,533 patients diagnosed with COPD (22%). Results: COPD was associated with a worse clinical presentation and an increased burden of comorbidities. At a median follow-up of 3.9 years, COPD was found to be an independent predictor of both predefined primary study end points, including all-cause mortality (HR 1.28, 95% CI 1.15-1.43, p < 0.0001) and all-cause mortality or hospitalization for cardiovascular reasons (HR 1.19, 95% CI 1.10-1.30, p < 0.0001). Both cardiovascular (HR 1.20, 95% CI 1.05-1.36, p = 0.007) and noncardiovascular mortality (HR 1.56, 95% CI 1.26-1.94, p < 0.0001) were significantly increased in COPD-HF patients, as well as hospitalizations for any reason (HR 1.23, 95% CI 1.14-1.34, p < 0.0001), for cardiovascular reasons (HR 1.16, 95% CI 1.06-1.27, p = 0.002) and for HF (HR 1.27, 95% CI 1.14-1.43, p < 0.0001). Conclusions: COPD is an independent predictor of mortality and hospitalizations in ambulatory HF patients. Increased awareness and improved management of COPD may reduce the burden of this morbidity to patients with HF.