Background: Individuals with α 1 -antitrypsin deficiency have increased elastase activity resulting in continuous degradation of elastin and early onset of COPD. Increased elastase activity may also affect elastic properties of the heart, which may impact risk of heart failure. We tested the hypothesis that α 1 -antitrypsin deficiency is associated with increased risk of heart failure in two large populations., Methods: In a nationwide nested study of 2209 patients with α 1 -antitrypsin deficiency and 21 869 controls without α 1 -antitrypsin deficiency matched on age, sex and municipality, we recorded admissions and deaths due to heart failure during a median follow-up of 62 years. We also studied a population-based cohort of another 102 481 individuals from the Copenhagen General Population Study including 187 patients from the Danish α 1 -Antitrypsin Deficiency Registry, all with genetically confirmed α 1 -antitrypsin deficiency., Results: Individuals with versus without α 1 -antitrypsin deficiency had increased risk of heart failure hospitalisation in the nationwide cohort (adjusted hazard ratio 2.64, 95% CI 2.25-3.10) and in the population-based cohort (1.77, 95% CI 1.14-2.74). Nationwide, these hazard ratios were highest in those without myocardial infarction (3.24, 95% CI 2.70-3.90), without aortic valve stenosis (2.80, 95% CI 2.38-3.29), without hypertension (3.44, 95% CI 2.81-4.22), without atrial fibrillation (3.33, 95% CI 2.75-4.04) and without any of these four diseases (6.00, 95% CI 4.60-7.82). Hazard ratios for heart failure-specific mortality in individuals with versus without α 1 -antitrypsin deficiency were 2.28 (95% CI 1.57-3.32) in the nationwide cohort and 3.35 (95% CI 1.04-10.74) in the population-based cohort., Conclusion: Individuals with α 1 -antitrypsin deficiency have increased risk of heart failure hospitalisation and heart failure-specific mortality in the Danish population., Competing Interests: Conflict of interest: B.G. Nordestgaard has consultancies with Amarin, Akcea, Amgen, AstraZeneca, Denka Seiken, Kowa, Novartis, Novo Nordisk and Silence Therap. Conflict of interest: No conflicts of interest exist for S.V. Winther, E.M. Landt, N. Seersholm and M. Dahl., (Copyright ©The authors 2023.)