ABSTRACT BACKGROUND: Data from long-term follow-up studies of well-characterised patients with asthma are limited. We studied all-cause and cause-specific mortality, and risk factors, in a large cohort of adults with asthma. METHODS: A total of 1.075 adult asthmatics were recruited consecutively from an out-patient clinic in 1974 to 1990, and followed up until the end of 2011. Subjects were classified as having allergic or non-allergic asthma on the basis of detailed history, spirometric tests, tests for IgE-mediated allergy (skin prick tests and RAST), and bronchial challenge tests. Information on vital status and cause of death were obtained from the Danish Death Register and the Danish National Board of Health. All-cause mortality was also studied in an age- and gender matched group of non-asthmatic subjects. RESULTS: All-cause mortality was significantly increased among asthmatics compared with controls (261 cases vs. 124 controls; relative risk (RR) 2.1, 95% confidence interval (CI) 1.4 to 3.0; p<0.001). The excess mortality was primarily due to death from obstructive lung disease (95 deaths). Subsequent death from asthma was significantly associated with age (p<0.001), level of FEV1 %pred (p<0.001), bronchodilator reversibility (p<0.01), peripheral eosinophil count (p<0.0001), and previous acute hospital contacts for asthma (p=0.002) at enrolment. No significant association was found between smoking habits and self-reported symptom-severity, and subsequent death from asthma. Non-allergic asthma was, after adjusting for age and level of FEV1 %pred, associated with a higher risk of death from asthma (RR 1.9, CI 1.1 to 3.2; p=0.001). CONCLUSION: This 25-year prospective study of a large cohort of well-characterised adults with asthma showed an excess mortality compared with matched controls to a large extent explained by death from obstructive lung disease.