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OBJECTIVES: Previous studies have indicated an association between shiftwork and coronary heart disease. The increased risk could be due to job strain, which could act as a mediator of disease. There is also a possibility that interaction between shiftwork and job strain could occur that may induce or modify the development of disease. We conducted this study to explore the relation between shiftwork, job strain, and myocardial infarction. METHODS: 2006 cases with acute first time myocardial infarction were compared with 2642 controls without symptoms of myocardial infarction, and obtained from the same population that gave rise to the cases (population based case-control study). RESULTS: Myocardial infarction risk was associated with shiftwork both in men (odds ratio (OR) 1.3, 95% confidence interval (95% CI) 1.1 to 1.6) and women (OR 1.3, 95% CI 0.9 to 1.8). In the age group 45-55, the relative risk was 1.6 in men and 3.0 in women. The results cannot be explained by job strain, age, job education level, or smoking. No interaction was found between shiftwork and job strain. CONCLUSIONS: The findings indicate that shiftwork is associated with myocardial infarction in both men and women. The mechanism is unclear, but the relation cannot be explained by job strain, smoking, or job education level.