ObjectivesThe prognostic utility of lifestyle risk factors and job-related conditions (LS&JRC) for cardiovascular disease (CVD) risk stratification remains to be clarified.MethodsWe investigated discrimination and clinical utility of LS&JRC among 2532 workers, 35–64 years old, CVD-free at the time of recruitment (1989–1996) in four prospective cohorts in Northern Italy, and followed up (median 14 years) until first major coronary event or ischemic stroke, fatal or non-fatal. From a Cox model including cigarette smoking, alcohol intake, occupational and sport physical activity and job strain, we estimated 10-year discrimination as the area under the ROC curve (AUC), and clinical utility as the Net Benefit.ResultsN = 162 events occurred during follow-up (10-year risk: 4.3%). The LS&JRC model showed the same discrimination (AUC = 0.753, 95% CI 0.700–0.780) as blood lipids, blood pressure, smoking and diabetes (AUC = 0.753), consistently across occupational classes. Among workers at low CVD risk (n = 1832, 91 CVD events), 687 were at increased LS&JRC risk; of these, 1 every 15 was a case, resulting in a positive Net Benefit (1.27; 95% CI 0.68–2.16).ConclusionsLS&JRC are as accurate as clinical risk factors in identifying future cardiovascular events among working males. Our results support initiatives to improve total health at work as strategies to prevent cardiovascular disease.