Background Individuals with α₁-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 α₁-antitrypsin deficiency is associated with increased risk of heart failure in two large populations. Methods In a nationwide nested study of 2209 patients with α₁-antitrypsin deficiency and 21 869 controls without α₁-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 α₁-Antitrypsin Deficiency Registry, all with genetically confirmed α₁-antitrypsin deficiency. Results Individuals with versus without α₁-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 α₁-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 α₁-antitrypsin deficiency have increased risk of heart failure hospitalisation and heart failure-specific mortality in the Danish population.