Breathlessness is a common presentation in primary care. To assess the long-term risk of diagnosed chronic obstructive pulmonary disease (COPD), asthma, ischaemic heart disease (IHD), and early mortality in patients with undiagnosed breathlessness. Matched cohort study using data from the UK Clinical Practice Research Datalink. Adults with first-recorded breathlessness between 1997 and 2010 and no prior diagnostic or prescription record for IHD or a respiratory disease ('exposed' cohort) were matched to individuals with no record of breathlessness ('unexposed' cohort). Analyses were adjusted for sociodemographic and comorbidity characteristics. In total, 75 698 patients (the exposed cohort) were followed for a median of 6.1 years, and more than one-third subsequently received a diagnosis of COPD, asthma, or IHD. In those who remained undiagnosed after 6 months, there were increased long-term risks of all three diagnoses compared with those in the unexposed cohort. Adjusted hazard ratios for COPD ranged from 8.6 (95% confidence interval [CI] = 6.8 to 11.0) for >6-12 months after the index date to 2.8 (95% CI = 2.6 to 3.0) for >36 months after the index date; asthma, 11.7 (CI = 9.4 to 14.6) to 4.3 (CI = 3.9 to 4.6); and IHD, 3.0 (CI = 2.7 to 3.4) to 1.6 (CI = 1.5 to 1.7). Risk of a longer time to diagnosis remained higher in members of the exposed cohort who had no relevant prescription in the first 6 months; approximately half of all future diagnoses were made for such patients. Risk of early mortality (all cause and disease specific) was higher in members of the exposed cohort. Breathlessness can be an indicator of developing COPD, asthma, and IHD, and is associated with early mortality. With careful assessment, appropriate intervention, and proactive follow-up and monitoring, there is the potential to improve identification at first presentation in primary care in those at high risk of future disease who present with this symptom. © British Journal of General Practice 2020.