The interplay of occupational and leisure time physical activity (LTPA) in affecting cardiovascular health is subject to debate. This study aimed to examine the independent and interacting associations of leisure time and occupational physical activity (OPA) with the incidence of coronary events within the BELSTRESS cohort. The study included 14,337 middle-aged men free from coronary heart disease at baseline. Standardized questionnaires and clinical examinations were used to assess socio-demographic factors, level of physical activity, job strain and classical coronary risk factors. The incidence of clinical coronary events was monitored during a mean follow-up time of 3.15 years. Results demonstrated overall a beneficial relation of LTPA and an adverse relation of physical work demands with cardiovascular health. However, an interaction effect between both physical activity types was observed, showing that men with high physical job demands who also engaged in physical activity during leisure time had an almost four times increased incidence of coronary events after adjusting for socio-demographic and classical coronary risk factors (HR 3.82; 95% CI 1.41-10.36). Stratified analyses revealed that moderate to high physical activity during leisure time was associated with a 60% reduced incidence rate of coronary events in men with low OPA (age adjusted HR 0.40; 95% CI 0.21-0.76), while this protective association was not observed in workers being exposed to high physical work demands (age adjusted HR 1.67; 95% CI 0.63-4.48). These findings suggest that recommendations regarding LTPA should be tailored according to the level of occupational physical activity.