Background: No previous long-term studies have examined if workers with low physical fitness have an increased risk of cardiovascular mortality due to long work hours. The aim of this study was to test this hypothesis. Methods: The study comprised 30-year follow-up of a cohort of 5249 gainfully employed men aged 40e59 years in the Copenhagen Male Study. 274 men with cardiovascular disease were excluded from the follow-up. Physical fitness (maximal oxygen consumption, Vo2max) was estimated using the Åstrand bicycle ergometer test, and number of work hours was obtained from questionnaire items; 4943 men were eligible for the incidence study. Results: 587 men (11.9%) died because of ischaemic heart disease (IHD). Cox analyses adjusted for age, blood pressure, smoking, alcohol, body mass index, diabetes, hypertension, physical work demands, and social class, showed that working more than 45 h/week was associated with an increased risk of IHD mortality in the least fit (Vo 2max range 15-26; HR 2.28, 95% CI 1.10 to 4.73), but not intermediate (Vo2max range 27-38; HR 0.94, 95% CI 0.59 to 1.51) and most fit men (Vo2max range 39-78; HR 0.91, 95% CI 0.41 to 2.02) referencing men working less than 40 h/week. Conclusions: The findings indicate that men with low physical fitness are at increased risk for IHD mortality from working long hours. Men working long hours should be physically fit.