ObjectivesWe examined the risk of disability retirement by smoking and physical activity, and particularly whether the risk due to smoking is affected by the level of physical activity. Additionally, the contribution of baseline health, sociodemographic and work-related factors to the joint associations of smoking and physical activity with disability retirement was considered.DesignCohort study.SettingHelsinki, Finland.ParticipantsEmployees of the City of Helsinki, aged 40–60 years at baseline in 2000–2002, were followed up using complete register data from the Finnish Centre of Pensions until the end of 2010 (n=6390, with a consent to register linkage from 74%).Primary outcome measureAll-cause disability retirement (ICD-10).ResultsAltogether, 608 employees (9.5%) retired due to disability during the follow-up. Cox regression models were fitted to examine the joint associations of smoking and physical activity with subsequent disability retirement. Never-smokers, ex-smokers and moderate smokers who were inactive or moderately active had an increased risk of disability retirement, but if they were vigorously active, they had no excess risk. Instead, all heavy smokers (15 or more cigarettes per day among women, and 20 or more among men), irrespective of physical activity, had an increased risk of disability retirement. The examined associations attenuated but remained for ex-smokers and heavy smokers after adjustments for gender, age, socioeconomic position, mental and physical workload, problem drinking, body mass index and self-rated health. No gender interactions were found.ConclusionsVigorous physical activity might help prevent disability retirement not only among never-smokers, but even among ex-smokers and moderate smokers. However, among heavy smokers, physical activity is not sufficient to eliminate the adverse effects of smoking on health and work ability.