BACKGROUND: Previous studies of non-smoking individuals with severe alpha(1)-antitrypsin deficiency (PiZZ) have been sparse and included only a limited number of individuals, mostly identified by respiratory symptoms. The aim of this study was to estimate the prognosis of non-smoking PiZZ individuals and to analyse the most common causes of death by including a large number of individuals who had been identified by other means than respiratory symptoms. METHODS: The study included 568 non-smoking PiZZ subjects who were selected from the Swedish National AAT Deficiency Registry and followed up from 1991 to September 2007. Of these, 156 (27%) were identified by respiratory symptoms (respiratory cases) and 412 were identified by extrapulmonary symptoms or screening (non-respiratory cases). RESULTS: 93 subjects (16%) died during the follow-up period. The specific standardised mortality rate (SMR) for the whole study population was 2.32 (95% CI 1.87 to 2.83) with no significant difference between men and women. The SMR was 2.55 (95% CI 1.91 to 2.83) for the respiratory cases and 2.07 (95% CI 1.49 to 2.81) for the non-respiratory cases. Further calculation of SMR for subgroups in the non-respiratory cases showed that the SMR was 0.70 (95% CI 0.14 to 2.04) for individuals identified by family/population screening. Emphysema and liver cirrhosis were the most common causes of death (45% and 28%, respectively). Malignant transformation was found in 38% of the cases with cirrhosis. CONCLUSION: Non-smoking PiZZ individuals identified by screening do not have an increased mortality risk compared with the Swedish general population.