Objectives: Previous studies indicated that stress diagnoses increase the risk of dementia. However, previous results may be biased by confounding, reverse causation and misclassification. Therefore, the main aim of this study was to investigate the association between clinically diagnosed stress in midlife and later dementia risk, while addressing limitations of previous studies.Methods: The study population was selected from all individuals in Denmark born 1935-1956. Individuals diagnosed with stress in midlife (aged 37-58 years) were matched (1:5) with individuals without stress diagnoses based on sex and birthdate (N = 103,484). Data were retrieved from national registers. Cox regression models were adjusted for socio-demographic factors and different morbidities.Results: We found a 2.20 (95% CI: 1.93-2.50) times higher rate of dementia among individuals with any stress diagnosis registered in midlife compared with no stress diagnosis. Hazard rate ratios of dementia were 1.73 (95% CI: 1.13-2.65) among individuals with acute stress reactions, 2.37 (95% CI: 2.05-2.74) among individuals with adjustment disorders, and 2.20 (95% CI: 1.73-2.80) among individuals with unspecified stress reactions. Individuals with PTSD and other stress reactions had non-significantly elevated rates of dementia. Adjustment for confounding only slightly attenuated the association, and reverse causation did not appear to bias the results substantially.Conclusion: Our results support the hypothesis that severe stress in midlife is an important risk factor for dementia. This finding emphasizes the importance of identifying and treating severe stress in midlife to reduce potential detrimental consequences for brain health in later life.