Objectives: To examine the relationships of late-career physical heaviness of work and sitting at work with mortality. A national-level job exposure matrix was used to determine the occupation-specific level of physical heaviness and sitting. - Design: Prospective cohort study between years 1990 and 2015. - Setting: Community. - Participants: 5210 men and 4725 women from the Helsinki Birth Cohort Study with an occupational code at baseline (ages 45–57 years). - Primary and secondary outcome measures: Total, cardiovascular (International Classification of Diseases 10th Revision I00–I99), cancer (C00–C97) and external (S00–Y84) mortality. - Results: The exposures, physical heaviness and sitting had a non-linear, inverse relationship. During the 26-year follow-up, 1536 men and 759 women died. Among men, physical heaviness of work was positively associated and sitting at work was negatively associated with allcause, cardiovascular and external cause mortality but they were not associated with cancer mortality. The HRs for men in the highest quartile of physical heaviness of work compared with men in the lowest quartile were 1.54 (1.31–1.80) for all-cause mortality, 1.70 (1.30–2.23) for cardiovascular mortality and 3.18 (1.75–5.78) for external cause mortality (adjusted for age and years of education). Compared with the lowest quartile, the HRs for the highest quartile of sitting at work among men were 0.71 (0.61–0.82) for all-cause mortality, 0.59 (0.45–0.77) for cardiovascular mortality and 0.38 (0.22–0.66) for external cause mortality. In women, neither physical heaviness of work nor sitting at work was associated with mortality. - Conclusions: Men in physically heavy work at their late-work career are at higher risk of death than men in physically light work.