The objective of this study was to investigate whether occupational gender segregation moderates the association between job stress in terms of effort-reward imbalance and the risk of myocardial infarction. This analysis was conducted in 1,381 cases and 1,697 referents of the Swedish SHEEP case control study aged 45-70 years. Information on myocardial infarction and biological coronary risk factors (e.g. hypertension, blood lipids) was achieved from clinical screenings. Information on socio-demographic variables, effort-reward imbalance, behavioral coronary risk factors (e.g., smoking), and additional coronary risk factors (e.g., diabetes, family history of coronary heart disease) was derived from well-tested standardized questionnaires. After adjustment for confounders the strongest association between overcommitment (the intrinsic component of effort-reward imbalance) and risk of belonging to the myocardial infarction group was found among women in male-dominated jobs (odds ratio [OR] = 2.71, 95% CI = 1.13-6.52) as compared to the remaining group (OR = 1.52, 95% CI = 1.01-2.31). Moreover, a significant interaction between pronounced overcommitment and male domination in relation to myocardial infarction was observed among women (OR = 2.44, 95% CI = 1.05-5.67). In men, an association between the ratio of effort and reward (the extrinsic component of the model) and risk of myocardial infarction was found for the majority, that is the group not working in women-dominated jobs (OR = 1.39, 95% CI = 1.04-1.86). Despite methodological limitations, this study gives preliminary evidence of a moderating effect of occupational gender segregation on the association of effort-reward imbalance (i.e., the intrinsic model component overcommitment) with acute myocardial infarction risk among women, but not among men.