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Objective To investigate the extent of the healthy-worker effect (HWE) on all-cause and cardiovascular disease (CVD) mortality, comparing population-based (PBC) and worker-based (WBC) cohorts.Material and Methods N=4700 men aged 30 to 59 at baseline were recruited from 1986 to 1994 in two PBCs (MONICA Brianza and PAMELA; n=2423) and in one WBC (SEMM; n=2277). We actively ascertained vital status (attrition rate: 5%) and retrieved death certificates (CVD mortality: ICD-9 codes 390-459 as main cause of death). HWE was estimated as the hazard ratio (HR) for a dummy indicator of WBC vs. PBC (reference) in age-adjusted Cox models. The HR was first computed in the full sample and then progressively restricted to ever-employed participants, workers, and salaried workers. Finally, stratified analyses were conducted by occupational class, dividing white/gold-collar and blue-collar salaried workers.Results In 23 years of median follow-up, we observed 670 all-cause and 161 CVD deaths. Crude all-cause and CVD-mortality rates (/1000 person-years) were 4.97 and 0.96 in WBC, and 8.39 and 2.24 in PBC, respectively. Age-adjusted HRs (95%CI) were 0.83 (0.70-0.97) for all-cause and 0.62 (0.44-0.88) for CVD mortality. When the analyses were restricted to employed salaried workers, HRs reduced to 0.98 (0.82-1.19) for all-cause and to 0.83 (0.55-1.24) for CVD mortality. In stratified analyses, blue-collar workers showed a potential HWE for CVD mortality only (HR: 0.63; 0.34-1.16).Conclusion When employment information is available, PBC can complement WBC in evaluating the relationship between occupational exposures and all-cause mortality.