Individuals in employment experience stress at work, and numerous epidemiological studies have documented its negative health effects, particularly on cardiovascular disease (CVD). Although evidence on the various interrelationships between work stress and CVD has been accumulated, those observations have not yet been conceptualized in terms of a life course perspective. Using the chain of risk model, we would like to propose a theoretical model incorporating six steps: (1) work stress increases the risk of incident CVD in healthy workers. (2) Among those whose work ability is not fully and permanently damaged, work stress acts as a determinant of the process of return to work after CVD onset. (3) CVD patients experience higher work stress after return to work. (4) Work stress increases the risk of recurrent CVD in workers with prior CVD. (5) CVD patients who fully lose their work ability transit to disability retirement. (6) Disability retirees due to CVD have an elevated risk of CVD mortality. The life course perspective might facilitate an in-depth understanding of the diverse interrelationships between work stress and CVD, thereby leading to work stress management interventions at each period of the lifespan and three-level prevention of CVD.