The aim of the study was to investigate the associations of occupational physical activity (OPA) and leisure-time physical activity (LTPA) with the risk of cardiovascular disease (CVD) and mortality. Physical activity data from the Baeck questionnaire was available for 1706 participants. During a follow-up period, there were 215 cases of CVD and 438 deaths. With the lowest tertile as the reference, the hazard ratios (HRs) for CVD and mortality in the highest tertiles of LTPA were 0.65 (95% confidence interval [CI] = 0.46-0.92) and 0.73 (95% CI = 0.58-0.92). In contrast, the HRs for CVD and mortality in the highest tertiles of OPA were 1.75 (95% CI = 1.10-2.80) and 1.53 (95% CI = 1.06-2.22). The association between OPA and the risk of CVD and mortality was significant in men but not in women. Our findings suggest that high OPA imposes harmful effects on the risk of CVD and mortality, particularly among men.