The objective of this study was to evaluate the association of physical activity at work with the risk of all-cause cardiovascular disease and cancer mortality. The cohort consisted of 3488 male, Israeli, industrial employees who participated in an 8-year follow-up study. During this period 129 deaths were recorded: 54 from cardiovascular disease, 47 from cancer, and 28 from other causes. Physical activity at work was assessed at entry on a 4-point scale (none, light, medium, and high). Potential confounding demographic, anthropometric, and socioeconomic variables, and health habits including leisure time physical activity were accounted for. We found that the hazard ratio of all-cause mortality in workers with a high physical workload was 1.82 (95% confidence interval, 1.18 to 2.81) compared with workers having a low workload. A similar trend was noted for cardiovascular disease and cancer mortality. We concluded that a high physical workload is associated with increased mortality rates. Future studies should differentiate between leisure time and work time physical activity.