Background: Incidence and prognosis for severe asthma–COPD overlap is poorly characterized. We investigated incidence and long-term outcome for patients with asthma–COPD overlap compared to asthma and COPD alone. Materials and methods: A total of 57,053 adults (aged 50–64 years) enrolled in the Danish Diet, Cancer, and Health cohort (1993–1997) were followed in the National Patients Registry for admissions for asthma (DJ45–46) and COPD (DJ40–44) and vital status. Asthma–COPD overlap was defined as at least one hospital admission for asthma and one for COPD (different time points), and incident asthma–COPD overlap as at least one of the diagnoses occurring after enrollment into the Diet, Cancer, and Health cohort. Results: A total of 1,845 (3.2%) and 4,037 (7.1%) participants had admissions for asthma and COPD, respectively, with 662 (1.2%) participants with asthma–COPD overlap. Incidence rate of asthma–COPD overlap per 1,000 person-years was higher in women (0.73) than in men (0.54) (P,0.02). Mortality rate was higher in asthma–COPD overlap (25.9 per 1,000 person-years) compared with COPD (23.1, P,0.05) and asthma (7.9, P,0.001) alone. Compared to COPD alone, mortality was higher in women with asthma–COPD overlap (19.6 and 25.5, respectively; P,0.01), and the excess mortality rate for asthma–COPD overlap patients was most prominent for younger age groups (12.9 compared to 7.2 and 4.6 for COPD and asthma alone, respectively; P,0.01). Conclusion: This large population-based study revealed a higher incidence of severe asthma– COPD overlap in women compared to men, and furthermore that all-cause mortality is higher in women and younger subjects with asthma–COPD overlap compared with those with asthma or COPD alone.