ObjectivesSocioeconomic inequalities have a strong impact on population health all over the world. Occupational status is a powerful determinant of health in rich societies. We aimed at investigating the association between occupation and mortality in a large metropolitan study.DesignCohort study.SettingRome, capital of Italy.ParticipantsWe used the Rome Longitudinal Study, the administrative cohort of residents in Rome at the 2001 general census, followed until 2015. We selected residents aged 15–65 years at baseline. For each subject, we had information on sex, age and occupation (occupational status and type of job) according to the Italian General Census recognition.Main outcome measuresWe investigated all-cause, cancer, cardiovascular and accidental mortality, major causes of death in the working-age population. We used Cox proportional hazards models to investigate the association between occupation and all-cause and cause-specific mortality in men and women.ResultsWe selected 1 466 726 subjects (52.1% women). 42 715 men and 29 915 women died during the follow-up. In men, 47.8% of deaths were due to cancer, 26.7% to cardiovascular causes and 6.4% to accidents, whereas in women 57.8% of deaths were due to cancer, 19.3% to cardiovascular causes and 3.5% to accidents. We found an association between occupational variables and mortality, more evident in men than in women. Compared with employed, unemployed had a higher risk of mortality for all causes with an HR=1.99 (95% CI 1.92 to 2.06) in men and an HR=1.49 (95% CI 1.39 to 1.60) in women. Compared with high-qualified non-manual workers, non-specialised manual workers had a higher mortality risk (HR=1.68, 95% CI 1.59 to 1.77 and HR=1.30, 95% CI 1.20 to 1.40, for men and women, respectively).ConclusionsThis study shows the importance of occupational variables as social health determinants and provides evidence for policy-makers on the necessity of integrated and preventive policies aimed at improving the safety of the living and the working environment.